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Archive for the ‘Longevity Genetics’ Category

Researchers Find Genetic Mutation That Encourages Longevity In Men – Yeshiva World News

Sunday, July 2nd, 2017

Researchers have found a mutation in the gene for the growth hormone receptor that promotes longevity, increasing mens lifespan by an average of 10 years.

This finding emerged from a new study led by Prof. Gil Atzmon of the University of Haifa. We were aware before that variants involved with genetic paths related to the growth hormone are also associated with longevity. Now we have found a specific variant whose presence or absence is directly connected to it, Prof. Atzmon explains.

Prof. Atzmon, head of the Laboratory of Genetics and Epigenetics of Aging and Longevity at the University of Haifa, and other colleagues at Albert Einstein College of Medicine have already found that dysfunction in the biological paths associated with the growth hormone and with insulin-like growth factor-1 (IGF-1) contribute to longevity. Until now, however, these paths were tested in the laboratory, and few mechanism responsible for this process had been identified in the human body.

In the present study, published in the journal Science Advances from the Science group, the researchers identified for the first time a genetic variation that modify the growth hormone function and encourages longevity in men. The initial research population (established by Professor Nir Barzilai at Einstein) comprised 102 American male Jews at the age of 100. The results were then compared with three additional populations of people at the age of 100 from around the world.

In all the groups, the deletion of exon 3 from the growth hormone receptor gene was found to be significantly more common among men (and not women) at the age of 100, compared to the control group of 70-year-olds. On average, people born with this variation lived ten years longer than those without it. According to Prof. Atzmon, this variation is certainly not the only reason for longevity, and many of the participants in the study survived beyond the age of 100 without this variation. However, the presence of the variant ensured longevity with virtual certainty.

The examination of the action of the variation showed that it has an unusual impact. In nature, lower strains of the same species usually live longer. For example, ponies live longer than horses, smaller breeds of dogs live longer than larger ones, and the same phenomenon is found among various rodents and insects. In this case, the variation in the receptor allowed the cells to absorb less growth hormone, however, when the hormone absorbed the protein expression was several times higher. The result: people born with the mutation who lived for around ten years more than others were also approximately 3 cm taller than those born without the receptor.

This study nicely wraps up the connection between growth hormone function and longevity. Our goal now is really to understand the mechanism of the variation we found, so that we can implement it and enable longevity while maintaining quality of life, Prof. Atzmon concluded.

(YWN Israel Desk, Jerusalem)

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Haifa U Researchers Find Genetic Mutation that Encourages Longevity in Men – The Jewish Press – JewishPress.com

Sunday, July 2nd, 2017

Photo Credit: Free image from Pixaboy

Researchers have found a mutation in the gene for the growth hormone receptor that promotes longevity, increasing mens lifespan by an average of 10 years. This finding emerged from a new study led by Prof. Gil Atzmon of the University of Haifa. We were aware before that variants involved with genetic paths related to the growth hormone are also associated with longevity. Now we have found a specific variant whose presence or absence is directly connected to it, Prof. Atzmon explains.

Prof. Atzmon, head of the Laboratory of Genetics and Epigenetics of Aging and Longevity at the University of Haifa, and other colleagues at Albert Einstein College of Medicine have already found that dysfunction in the biological paths associated with the growth hormone and with insulin-like growth factor-1 (IGF-1) contribute to longevity. Until now, however, these paths were tested in the laboratory, and few mechanism responsible for this process had been identified in the human body.

In the present study, published in the journal Science Advances from the Science group, the researchers identified for the first time a genetic variation that modify the growth hormone function and encourages longevity in men. The initial research population (established by Professor Nir Barzilai at Einstein) comprised 102 American male Jews at the age of 100. The results were then compared with three additional populations of people at the age of 100 from around the world.

In all the groups, the deletion of exon 3 from the growth hormone receptor gene was found to be significantly more common among men (and not women) at the age of 100, compared to the control group of 70-year-olds. On average, people born with this variation lived ten years longer than those without it. According to Prof. Atzmon, this variation is certainly not the only reason for longevity, and many of the participants in the study survived beyond the age of 100 without this variation. However, the presence of the variant ensured longevity with virtual certainty.

The examination of the action of the variation showed that it has an unusual impact. In nature, lower strains of the same species usually live longer. For example, ponies live longer than horses, smaller breeds of dogs live longer than larger ones, and the same phenomenon is found among various rodents and insects. In this case, the variation in the receptor allowed the cells to absorb less growth hormone, however, when the hormone absorbed the protein expression was several times higher. The result: people born with the mutation who lived for around ten years more than others were also approximately 3 cm taller than those born without the receptor.

This study nicely wraps up the connection between growth hormone function and longevity. Our goal now is really to understand the mechanism of the variation we found, so that we can implement it and enable longevity while maintaining quality of life, Prof. Atzmon concluded.

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Haifa U Researchers Find Genetic Mutation that Encourages Longevity in Men - The Jewish Press - JewishPress.com

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68-Year Study: Childhood Intelligence and Longevity Related – Newsmax

Sunday, July 2nd, 2017

Smart children tend to live longer than their less intelligent peers, a new study suggests.

The analysis by Scottish researchers, published by medical journal BMJ, tracked 75,252 men and women born in 1936 who had taken standardized intelligence tests in 1947.

By 2015, researchers confirmed a cause of death for 25,979 of them; 30,464 were still living in Britain.

"In a whole national population year of birth cohort followed over the life course from age 11 to age 79, higher scores on a well validated childhood intelligence test were associated with lower risk of mortality ascribed to coronary heart disease and stroke, cancers related to smoking (particularly lung and stomach), respiratory diseases, digestive diseases, injury, and dementia," the researchers wrote.

According to The New York Times, even after controlling for smoking, the link to lower scores on the intelligence testsdidn't disappear. The study found no association of lower intelligence with cancers unrelated to smoking or with suicide, but there was a strong association with death by accidental injury.

"We dont know yet why intelligence from childhood and longevity are related, and we are keeping an open mind," senior author, Ian Deary of the University of Edinburgh told the Times.

"Lifestyles, education, deprivation and genetics may all play a part."

2017 Newsmax. All rights reserved.

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Lamarckism – Wikipedia

Thursday, January 5th, 2017

Lamarckism (or Lamarckian inheritance) is the idea that an organism can pass on characteristics that it has acquired during its lifetime to its offspring (also known as heritability of acquired characteristics or soft inheritance). It is named after the French biologist Jean-Baptiste Lamarck (17441829), who incorporated the action of soft inheritance into his evolutionary theories as a supplement to his concept of an inherent progressive tendency driving organisms continuously towards greater complexity, in parallel but separate lineages with no extinction. Lamarck did not originate the idea of soft inheritance, which proposes that individual efforts during the lifetime of the organisms were the main mechanism driving species to adaptation, as they supposedly would acquire adaptive changes and pass them on to offspring.

When Charles Darwin published his theory of evolution by natural selection in On the Origin of Species (1859), he continued to give credence to what he called "use and disuse inheritance," but rejected other aspects of Lamarck's theories. Later, Mendelian genetics supplanted the notion of inheritance of acquired traits, eventually leading to the development of the modern evolutionary synthesis, and the general abandonment of the Lamarckian theory of evolution in biology. Despite this abandonment, interest in Lamarckism has continued as studies in the field of epigenetics have highlighted the possible inheritance of behavioral traits acquired by the previous generation.[1][2][3][4][5] However, this remains controversial as science historians have asserted that it is inaccurate to describe transgenerational epigenetic inheritance as a form of Lamarckism.[6][7][8][9]

Between 1794 and 1796 Erasmus Darwin wrote Zoonomia suggesting "that all warm-blooded animals have arisen from one living filament... with the power of acquiring new parts" in response to stimuli, with each round of "improvements" being inherited by successive generations.[10] Subsequently, Jean-Baptiste Lamarck repeated in his Philosophie Zoologique of 1809 the folk wisdom that characteristics which were "needed" were acquired (or diminished) during the lifetime of an organism then passed on to the offspring. He incorporated this mechanism into his thoughts on evolution, seeing it as resulting in the adaptation of life to local environments.

Lamarck founded a school of French Transformationism which included tienne Geoffroy Saint-Hilaire, and which corresponded with a radical British school of anatomy based in the extramural anatomy schools in Edinburgh, Scotland, which included the surgeon Robert Knox and the comparative anatomist Robert Edmond Grant. In addition, the Regius Professor of Natural History at the University of Edinburgh, Robert Jameson, was the probable author of an anonymous paper in 1826 praising "Mr. Lamarck" for explaining how the higher animals had "evolved" from the "simplest worms"this was the first use of the word "evolved" in a modern sense. As a young student, Charles Darwin was tutored by Grant, and worked with him on marine creatures.

The Vestiges of the Natural History of Creation, authored by Robert Chambers in St Andrews, Scotland, and published anonymously in England in 1844, proposed a theory which combined radical phrenology with Lamarckism, causing political controversy for its radicalism and unorthodoxy, but exciting popular interest and preparing a huge and prosperous audience for Darwin.

Darwin's On the Origin of Species proposed natural selection as the main mechanism for development of species, but did not rule out a variant of Lamarckism as a supplementary mechanism.[11] Darwin called his Lamarckian hypothesis pangenesis, and explained it in the final chapter of his book The Variation of Animals and Plants under Domestication (1868), after describing numerous examples to demonstrate what he considered to be the inheritance of acquired characteristics. Pangenesis, which he emphasised was a hypothesis, was based on the idea that somatic cells would, in response to environmental stimulation (use and disuse), throw off 'gemmules' or 'pangenes' which travelled around the body (though not necessarily in the bloodstream). These pangenes were microscopic particles that supposedly contained information about the characteristics of their parent cell, and Darwin believed that they eventually accumulated in the germ cells where they could pass on to the next generation the newly acquired characteristics of the parents. Darwin's half-cousin, Francis Galton, carried out experiments on rabbits, with Darwin's cooperation, in which he transfused the blood of one variety of rabbit into another variety in the expectation that its offspring would show some characteristics of the first. They did not, and Galton declared that he had disproved Darwin's hypothesis of pangenesis, but Darwin objected, in a letter to the scientific journal Nature, that he had done nothing of the sort, since he had never mentioned blood in his writings. He pointed out that he regarded pangenesis as occurring in Protozoa and plants, which have no blood.[12]

The identification of Lamarckism with the inheritance of acquired characteristics is regarded by some as an artifact of the subsequent history of evolutionary thought, repeated in textbooks without analysis. American paleontologist and historian of science Stephen Jay Gould wrote that in the late 19th century, evolutionists "re-read Lamarck, cast aside the guts of it ... and elevated one aspect of the mechanicsinheritance of acquired charactersto a central focus it never had for Lamarck himself."[13] He argued that "the restriction of 'Lamarckism' to this relatively small and non-distinctive corner of Lamarck's thought must be labelled as more than a misnomer, and truly a discredit to the memory of a man and his much more comprehensive system."[14] Gould advocated defining "Lamarckism" more broadly, in line with Lamarck's overall evolutionary theory.

Lamarck incorporated two ideas into his theory of evolution, in his day considered to be generally true. The first was the idea of use versus disuse; he theorized that individuals lose characteristics they do not require, or use, and develop characteristics that are useful. His second point was to argue that the acquired traits were heritable. Examples of what is traditionally called "Lamarckism" would include the idea that when giraffes stretch their necks to reach leaves high in trees (especially Acacias), they strengthen and gradually lengthen their necks. These giraffes have offspring with slightly longer necks (also known as "soft inheritance"). Similarly, a blacksmith, through his work, strengthens the muscles in his arms, and thus his sons will have similar muscular development when they mature.

Lamarck stated the following two laws:

English translation:

In essence, a change in the environment brings about change in "needs" (besoins), resulting in change in behavior, bringing change in organ usage and development, bringing change in form over timeand thus the gradual transmutation of the species.

However, as historians of science such as Michael Ghiselin and Stephen Jay Gould have pointed out, none of these views were original to Lamarck.[17][18] On the contrary, Lamarck's contribution was a systematic theoretical framework for understanding evolution. He saw evolution as comprising two processes;

The idea that germline cells contain information that passes to each generation unaffected by experience and independent of the somatic (body) cells, came to be referred to as the Weismann barrier, and is frequently quoted as putting a final end to Lamarckism and theory of inheritance of acquired characteristics.

August Weismann conducted the experiment of removing the tails of 68 white mice, repeatedly over five generations, and reporting that no mice were born in consequence without a tail or even with a shorter tail. He stated that "901 young were produced by five generations of artificially mutilated parents, and yet there was not a single example of a rudimentary tail or of any other abnormality in this organ."[19]

However, the experiment has been questioned in relationship to Lamarck's hypothesis as it did not address the use and disuse of characteristics in response to the environment. Biologist Peter Gauthier noted that:

Can Weismann's experiment be considered a case of disuse? Lamarck proposed that when an organ was not used, it slowly, and very gradually atrophied. In time, over the course of many generations, it would gradually disappear as it was inherited in its modified form in each successive generation. Cutting the tails off mice does not seem to meet the qualifications of disuse, but rather falls in a category of accidental misuse... Lamarck's hypothesis has never been proven experimentally and there is no known mechanism to support the idea that somatic change, however acquired, can in some way induce a change in the germplasm. On the other hand it is difficult to disprove Lamarck's idea experimentally, and it seems that Weismann's experiment fails to provide the evidence to deny the Lamarckian hypothesis, since it lacks a key factor, namely the willful exertion of the animal in overcoming environmental obstacles.[20]

Science historian Michael Ghiselin also considers the Weismann tail-chopping experiment to have no bearing on the Lamarckian hypothesis:

The acquired characteristics that figured in Lamarck's thinking were changes that resulted from an individual's own drives and actions, not from the actions of external agents. Lamarck was not concerned with wounds, injuries or mutilations, and nothing that Lamarck had set forth was tested or "disproven" by the Weismann tail-chopping experiment.[17]

The period of the history of evolutionary thought between Darwin's death in the 1880s, and the foundation of population genetics in the 1920s and beginnings of modern evolutionary synthesis in the 1930s, is called the eclipse of Darwinism by some historians of science. During that time many scientists and philosophers accepted the reality of evolution but doubted whether natural selection was the main evolutionary mechanism.[21]

Among the most popular alternatives were theories involving the inheritance of characteristics acquired during an organism's lifetime. Scientists who felt that such Lamarckian mechanisms were the key to evolution were called neo-Lamarckians and included the British botanist George Henslow (18351925), who studied the effects of environmental stress on the growth of plants, in the belief that such environmentally-induced variation might explain much of plant evolution, and the American entomologist Alpheus Spring Packard, Jr., who studied blind animals living in caves and wrote a book in 1901 about Lamarck and his work.[22][23]

Also included were a number of paleontologists like Edward Drinker Cope and Alpheus Hyatt, who felt that the fossil record showed orderly, almost linear, patterns of development that they felt were better explained by Lamarckian mechanisms than by natural selection. Some people, including Cope and the Darwin critic Samuel Butler, felt that inheritance of acquired characteristics would let organisms shape their own evolution, since organisms that acquired new habits would change the use patterns of their organs, which would kick-start Lamarckian evolution. They considered this philosophically superior to Darwin's mechanism of random variation acted on by selective pressures. Lamarckism also appealed to those, like the philosopher Herbert Spencer and the German anatomist Ernst Haeckel, who saw evolution as an inherently progressive process.[22] The German zoologist Theodor Eimer combined Larmarckism with ideas about orthogenesis.[24]

With the development of the modern synthesis of the theory of evolution and a lack of evidence for a mechanism for acquiring and passing on new characteristics, or even their heritability, Lamarckism largely fell from favor. Unlike neo-Darwinism, the term neo-Lamarckism refers more to a loose grouping of largely heterodox theories and mechanisms that emerged after Lamarck's time, than to any coherent body of theoretical work.

In a series of experiments from 1869 to 1891, Charles-douard Brown-Squard cut the sciatic nerve of the leg and spinal cord in the dorsal regions of guinea pigs, causing an abnormal nervous condition resembling epilepsy; these were then bred and produced epileptic offspring.[25] Although some scientists considered this evidence for Lamarckian inheritance, the experiments were not Lamarckian, as they did not address the use and disuse of characteristics in response to the environment.[26] The results from the experiment were not duplicated by other scientists.[27] One explanation for the results was that they show a transmitted disease, and not evidence for the inheritance of an acquired characteristic.[28] Brown-Squard's experiments are now considered anomalous and alternative explanations have been suggested.[29]

The French botanist Gaston Bonnier, conducting experiments in the French Alps in 1884 and the Pyrenees in 1886, studied structural changes induced by growing plants at various altitudes and transplanting them to others. Bonnier believed he had proven acquired adaptive characteristics; however, he did not weed, cultivate, fertilize or protect his plant specimens from native vegetation. In the 1920s his experiments were analysed and attributed to genetic contamination rather than Lamarckian inheritance.[30]

In a series of experiments (in 1891, 1893 and 1895) on the action of light on the coloration of flatfish, the British marine biologist Joseph Thomas Cunningham (18591935) directed light upon the lower sides of flatfishes by means of a glass-bottomed tank placed over a mirror. He discovered the influence of light in producing pigments on the lower sides of flatfishes and gave his results a Lamarckian interpretation.[31][32][33] Other scientists wrote that Cunningham had received some definite results, but that they were open to more than one interpretation.[34] The geneticist William Bateson was not convinced that the cause of the increase in pigmentation was from the illumination. George Romanes wrote approvingly of Cunningham's interpretation.[35]Thomas Hunt Morgan criticized the experiments and did not believe the results were evidence for Lamarckism.[36]

In 1906, the philosopher Eugenio Rignano wrote a book, Sur La Transmissibilit Des Caractres Acquis, that argued for the inheritance of acquired characteristics.[37] He advanced a moderated Lamarckian hypothesis of inheritance known as "centro-epigenesis."[38][39] However, his views were controversial and not accepted by the majority in the scientific community.[40]

In a series of experiments from 1907 to 1910, William Lawrence Tower performed experiments on potato beetles which were said by Ernest MacBride to have provided evidence for the inheritance of acquired characteristics.[41] These were heavily criticized by William Bateson.[42] It was later suggested that his research may have been faked.[43] Tower claimed that the records of his experimental results had been lost in a fire.[44] The geneticist William E. Castle who visited Tower's laboratory was not impressed by the experimental conditions. He later concluded that Tower had faked his data. Castle found the fire suspicious and also Tower's claim that a steam leak in his greenhouse had destroyed all his beetle stocks.[45]

Experiments conducted by Gustav Tornier from 1907 to 1918 on goldfish and embryos of frogs and newts were supported by neo-Lamarckians such as Cunningham and MacBride as demonstrating the inheritance of acquired characteristics.[46][47] The abnormalities were interpreted as the result of an osmotic effect by other researchers.[48]

In the late 19th century, Frederick Merrifield exposed caterpillars and chrysalids to significantly high and low temperatures, and discovered permanent changes in some offspring's wing patterns. Swiss biologist Maximilian Rudolph Standfuss (18541917) led 30 years of intensive breeding experiments with European butterflies and after several generations, found similar preserved variations even generations after the cessation of exposing them to low temperatures.[49] Standfuss was a neo-Lamarckian and attributed the results of his experiments as direct changes to the environment.[50] In 1940, Richard Goldschmidt interpreted these results without invoking Lamarckian inheritance, and in 1998 Ernst Mayr wrote that results reported by Standfuss and others on the effects of abnormal temperatures on Lepidoptera are difficult to interpret.[51]

In 1910, the American zoologist Charles Rupert Stockard (18791939) tested the effects of alcohol intoxication on the offspring of pregnant guinea pigs. Stockard discovered that repeated alcohol intoxication in the guinea pigs produced defects and malformations in their offspring that was passed down to two or more generations. His results were challenged by the biologist Raymond Pearl who performed the same experiments with chickens.[52] Pearl discovered that the offspring of the chickens that had been exposed to alcohol were not defected but were healthy. He attributed his findings to the detrimental effects of alcohol only on the eggs and sperm which were already weak, the strong eggs and sperm were unaffected by alcohol intoxication. Pearl argued that his results had a Darwinian, not a Lamarckian explanation.[52]

The French zoologist Yves Delage in his book The Theories of Evolution (1912) reviewed experiments into Lamarckism concluded the evidence "is not of uniform value and is more or less open to criticism; very little of it is convincing... [due to] difficulties of experimentation and, above all, of interpretation."[53]

In a series of experiments, Francis Bertody Sumner (18741945) reared several generations of white mice under different conditions of temperature and relative humidity.[54] Sumner discovered that the white mice at 20C to 30C developed longer bodies, tails and hind feet which were also transmitted to their offspring over a number of generations, however, later results were not entirely consistent and the experiments ended in uncertainty.[55]

Between 1918 and 1924, two American scientists Michael F. Guyer and Elizabeth A. Smith performed experiments in which fowl serum antibodies for rabbit lens-protein were injected into pregnant rabbits which resulted in defects in the eyes of some of their offspring that were inherited through eight generations.[56] Their experiments were criticized and were not repeated by other scientists.[57]

In the 1920s, experiments by Paul Kammerer on amphibians, particularly the midwife toad, appeared to find evidence supporting Lamarckism. However, his specimens with supposedly acquired black foot-pads were found to have been tampered with. In The Case of the Midwife Toad (1971), author and journalist Arthur Koestler surmised that the tampering had been done by a Nazi sympathiser to discredit Kammerer for his political views, and that his research might actually have been valid. However, most biologists believe that Kammerer was a fraud, and even among those who believe he was honest, most believe that he misinterpreted the results of his experiments.[58]

During the 1920s, Harvard University researcher William McDougall studied the abilities of rats to correctly solve mazes. He found that offspring of rats that had learned the maze were able to run it faster. The first rats would get it wrong 165 times before being able to run it perfectly each time, but after a few generations it was down to 20. McDougall attributed this to some sort of Lamarckian evolutionary process.[59]Oscar Werner Tiegs and Wilfred Eade Agar later showed McDougall's results to be incorrect, caused by poor experimental controls.[60][61]Peter Medawar wrote that "careful and extensive repetitions of McDougall's research failed altogether to confirm it. His work therefore becomes an exhibit in the capacious ill-lit museum of unreproducible phenomena."[62]

In the 1920s, John William Heslop-Harrison conducted experiments on the peppered moth, claiming to have evidence for the inheritance of acquired characteristics. Other scientists failed to replicate his results.[63][64] The Russian physiologist Ivan Pavlov claimed to have observed a similar phenomenon in white mice being subject to a conditioned reflex experiment involving food and the sound of a bell. He wrote that with each generation, the mice became easier to condition. In 1926, Pavlov announced that there had been a fatal flaw in his experiment and retracted his claim to have demonstrated Lamarckian inheritance.[65] Other researchers were also unable to replicate his results.[66]

In other experiments, Coleman Griffith (1920, 1922) and John Detlefson (1923, 1925) reared rats in cages on a rotating table for three months. The rats adapted to the rotating condition to such an extent that when the rotation was stopped they showed signs of disequilibration and other physiological conditions which were inherited for several generations.[67][68][69][70] In 1933, Roy Dorcus replicated their experiments but obtained different results as the rotated rats did not manifest any abnormalities of posture described by Griffith and Detlefson.[71] Other studies revealed that the same abnormalities could occur in rats without rotation if they were suffering from an ear infection thus the results were interpreted as a case of infection, not Lamarckian inheritance.[72]

In the 1930s, the German geneticist Victor Jollos (18871941) in a series of experiments claimed evidence for inherited changes induced by heat treatment in Drosophila melanogaster.[73] His experiments were described as Lamarckian. However, Jollos was not an advocate of Lamarckian evolution and attributed the results from his experiments as evidence for directed mutagenesis. American scientists were unable to replicate his results.[74]

The British anthropologist Frederic Wood Jones and the South African paleontologist Robert Broom supported a neo-Lamarckian view of human evolution as opposed to the Darwinian view. The German anthropologist Hermann Klaatsch relied on a neo-Lamarckian model of evolution to try and explain the origin of bipedalism. Neo-Lamarckism remained influential in biology until the 1940s when the role of natural selection was reasserted in evolution as part of the modern evolutionary synthesis.[75]

Herbert Graham Cannon, a British zoologist, defended Lamarckism in his 1959 book Lamarck and Modern Genetics.[76]

In the 1960s, "biochemical Lamarckism" was advocated by the embryologist Paul Wintrebert.[77]

In the 1970s, Australian immunologist Edward J. Steele and colleagues proposed a neo-Lamarckian mechanism to try to explain why homologous DNA sequences from the VDJ gene regions of parent mice were found in their germ cells and seemed to persist in the offspring for a few generations. The mechanism involved the somatic selection and clonal amplification of newly acquired antibody gene sequences that were generated via somatic hypermutation in B-cells. The messenger RNA (mRNA) products of these somatically novel genes were captured by retroviruses endogenous to the B-cells and were then transported through the bloodstream where they could breach the soma-germ barrier and retrofect (reverse transcribe) the newly acquired genes into the cells of the germ line. Although Steele was advocating this theory for the better part of two decades, little more than indirect evidence was ever acquired to support it. An interesting attribute of this idea is that it strongly resembles Darwin's own theory of pangenesis, except in the soma to germ line feedback theory, pangenes are replaced with realistic retroviruses.[78] Regarding Steele's research, historian of biology Peter J. Bowler wrote, "his work was bitterly criticized at the time by biologists who doubted his experimental results and rejected his hypothetical mechanism as implausible."[79]

Neo-Lamarckism was dominant in French biology for more than a century. French scientists who supported neo-Lamarckism included Edmond Perrier (18441921), Alfred Giard (18461908), Gaston Bonnier (18531922) and Pierre-Paul Grass (18951985).[80]

In 1987, Ryuichi Matsuda coined the term "pan-environmentalism" for his evolutionary theory which he saw as a fusion of Darwinism with neo-Lamarckism. He held that heterochrony is a main mechanism for evolutionary change and that novelty in evolution can be generated by genetic assimilation.[81][82] His views were criticized by Arthur M. Shapiro for providing no solid evidence for his theory. Shapiro noted that "Matsuda himself accepts too much at face value and is prone to wish-fulfilling interpretation."[82]

Within the discipline of history of technology, Lamarckism has been used in linking cultural development to human evolution by classifying artefacts as extensions of human anatomy: in other words, as the acquired cultural characteristics of human beings. Ben Cullen has shown that a strong element of Lamarckism exists in sociocultural evolution.[83]

A form of Lamarckism was revived in the Soviet Union of the 1930s when Trofim Lysenko promoted Lysenkoism which suited the ideological opposition of Joseph Stalin to genetics. This ideologically driven research influenced Soviet agricultural policy which in turn was later blamed for crop failures.[84]

Neo-Lamarckian versions of evolution were widespread in the late 19th century. The idea that living things could to some degree choose the characteristics that would be inherited allowed them things to be in charge of their own destiny as opposed to the Darwinian view, which made them puppets at the mercy of the environment. Such ideas were more popular than natural selection in the late 19th century as it made it possible for biological evolution to fit into a framework of a divine or naturally willed plan, thus the neo-Lamarckian view of evolution was often advocated by proponents of orthogenesis.[85] According to Peter J. Bowler:

One of the most emotionally compelling arguments used by the neo-Lamarckians of the late nineteenth century was the claim that Darwinism was a mechanistic theory which reduced living things to puppets driven by heredity. The selection theory made life into a game of Russian roulette, where life or death was predetermined by the genes one inherited. The individual could do nothing to mitigate bad heredity. Lamarckism, in contrast, allowed the individual to choose a new habit when faced with an environmental challenge and shape the whole future course of evolution.[86]

Supporters of neo-Lamarckism such as George Bernard Shaw and Arthur Koestler claimed that Lamarckism is more humane and optimistic than Darwinism.[87]

George Gaylord Simpson in his book Tempo and Mode in Evolution (1944) claimed that experiments in heredity have failed to corroborate any Lamarckian process.[88] Simpson noted that neo-Lamarckism "stresses a factor that Lamarck rejected: inheritance of direct effects of the environment" and neo-Lamarckism is closer to Darwin's pangenesis than Lamarck's views.[89] Simpson wrote, "the inheritance of acquired characters, failed to meet the tests of observation and has been almost universally discarded by biologists."[90]

Botanist Conway Zirkle pointed out that Lamarck did not originate the hypothesis that acquired characters were heritable, therefore it is incorrect to refer to it as Lamarckism:

What Lamarck really did was to accept the hypothesis that acquired characters were heritable, a notion which had been held almost universally for well over two thousand years and which his contemporaries accepted as a matter of course, and to assume that the results of such inheritance were cumulative from generation to generation, thus producing, in time, new species. His individual contribution to biological theory consisted in his application to the problem of the origin of species of the view that acquired characters were inherited and in showing that evolution could be inferred logically from the accepted biological hypotheses. He would doubtless have been greatly astonished to learn that a belief in the inheritance of acquired characters is now labeled "Lamarckian," although he would almost certainly have felt flattered if evolution itself had been so designated.[91]

Peter Medawar wrote regarding Lamarckism, "very few professional biologists believe that anything of the kind occursor can occurbut the notion persists for a variety of nonscientific reasons." Medawar stated there is no known mechanism by which an adaption acquired in an individual's lifetime can be imprinted on the genome and Lamarckian inheritance is not valid unless it excludes the possibility of natural selection but this has not been demonstrated in any experiment.[92]

Martin Gardner wrote in his book Fads and Fallacies in the Name of Science (1957):

A host of experiments have been designed to test Lamarckianism. All that have been verified have proved negative. On the other hand, tens of thousands of experiments reported in the journals and carefully checked and rechecked by geneticists throughout the world have established the correctness of the gene-mutation theory beyond all reasonable doubt... In spite of the rapidly increasing evidence for natural selection, Lamarck has never ceased to have loyal followers.... There is indeed a strong emotional appeal in the thought that every little effort an animal puts forth is somehow transmitted to his progeny.[93]

According to Ernst Mayr, any Lamarckian theory involving the inheritance of acquired characters has been refuted as "DNA does not directly participate in the making of the phenotype and that the phenotype, in turn, does not control the composition of the DNA."[94] Peter J. Bowler has written that although many early scientists took Lamarckism seriously, it was discredited by genetics in the early twentieth century.[95]

Forms of 'soft' or epigenetic inheritance within organisms have been suggested as neo-Lamarckian in nature by such scientists as Eva Jablonka and Marion J. Lamb. In addition to 'hard' or genetic inheritance, involving the duplication of genetic material and its segregation during meiosis, there are other hereditary elements that pass into the germ cells also.[96] These include things like methylation patterns in DNA and chromatin marks, both of which regulate the activity of genes. These are considered Lamarckian in the sense that they are responsive to environmental stimuli and can differentially affect gene expression adaptively, with phenotypic results that can persist for many generations in certain organisms.[97]

Jablonka and Lamb have called for an extended evolutionary synthesis. They have argued that there is evidence for Lamarckian epigenetic control systems causing evolutionary changes and the mechanisms underlying epigenetic inheritance can also lead to saltational changes that reorganize the epigenome.[98]

Interest in Lamarckism has increased, as studies in the field of epigenetics have highlighted the possible inheritance of behavioral traits acquired by the previous generation.[96] A 2009 study examined foraging behavior in chickens as a function of stress:

Transmissions of information across generations which does not involve traditional inheritance of DNA-sequence alleles is often referred to as soft inheritance [99] or "Lamarckian inheritance."[100]

The study concluded:

Our findings suggest that unpredictable food access caused seemingly adaptive responses in feeding behavior, which may have been transmitted to the offspring by means of epigenetic mechanisms, including regulation of immune genes. This may have prepared the offspring for coping with an unpredictable environment.[100]

The evolution of acquired characteristics has also been shown in human populations who have experienced starvation, resulting in altered gene function in both the starved population and their offspring.[101] The process of DNA methylation is thought to be behind such changes.

In October 2010, further evidence linking food intake to traits inherited by the offspring were shown in a study of rats conducted by several Australian universities.[102] The study strongly suggested that fathers can transfer a propensity for obesity to their daughters as a result of the fathers' food intake, and not their genetics (or specific genes), prior to the conception of the daughter. A "paternal high-fat diet" was shown to cause cell dysfunction in the daughter, which in turn led to obesity for the daughter. Felicia Nowak, et al. reported at the Endocrine Society meeting in June 2013 that obese male rats passed on the tendency to obesity to their male offspring.[103]

Several studies, one conducted by researchers at Massachusetts Institute of Technology and another by researchers at the Tufts University School of Medicine, have rekindled the debate once again. As reported in MIT Technology Review in February 2009, "The effects of an animal's environment during adolescence can be passed down to future offspring ... The findings provide support for a 200-year-old theory of evolution that has been largely dismissed: Lamarckian evolution, which states that acquired characteristics can be passed on to offspring."[104] A report investigating the inheritance of resistance to viral infection in the nematode Caenorhabditis elegans suggests that small RNA molecules may be inherited in a non-Mendelian fashion and provide resistance to infection.[105] More recent studies in C. elegans have revealed that progeny may inherit information regarding environmental challenges that the parent experienced, such as starvation, and that this epigenetic effect may persist for multiple generations.[106]

A study (Akimoto et al. 2007) on epigenetic inheritance in rice plants came to the conclusion that "gene expression is flexibly tuned by methylation, allowing plants to gain or lose particular traits which are heritable as far as methylation patterns of corresponding genes are maintained. This is in support of the concept of Lamarckian inheritance, suggesting that acquired traits are heritable."[107] Another study (Sano, 2010) wrote that observations suggest that acquired traits are heritable in plants as far as the acquired methylation pattern is stably transmitted which is consistent with Lamarckian evolution.[108] Handel and Ramagopalan found that there is evidence that epigenetic alterations such as DNA methylation and histone modifications are transmitted transgenerationally as a mechanism for environmental influences to be passed from parents to offspring. According to Handel and Romagopalan "epigenetics allows the peaceful co-existence of Darwinian and Lamarckian evolution."[109]

In their book An Introduction to Zoology (2013), Joseph Springer and Dennis Holley wrote:

Lamarck and his ideas were ridiculed and discredited. In a strange twist of fate, Lamarck may have the last laugh. Epigenetics, an emerging field of genetics, has shown that Lamarck may have been at least partially correct all along. It seems that reversible and heritable changes can occur without a change in DNA sequence (genotype) and that such changes may be induced spontaneously or in response to environmental factorsLamarck's "acquired traits." Determining which observed phenotypes are genetically inherited and which are environmentally induced remains an important and ongoing part of the study of genetics, developmental biology, and medicine.[110]

Eugene Koonin has written that the prokaryotic CRISPR system and Piwi-interacting RNA could be classified as Lamarckian and came to the conclusion that "Both Darwinian and Lamarckian modalities of evolution appear to be important, and reflect different aspects of the interaction between populations and the environment."[111]

A study in 2013 reported that mutations caused by a father's lifestyle can be inherited by his children through multiple generations.[112] A study from Lund University in Sweden showed that exercise changes the epigenetic pattern of genes that affect fat storage in the body.[113]

Commenting on this, Charlotte Ling explained:

The cells of the body contain DNA, which contains genes. We inherit our genes and they cannot be changed. The genes, however, have 'methyl groups' attached which affect what is known as 'gene expression' whether the genes are activated or deactivated. The methyl groups can be influenced in various ways, through exercise, diet and lifestyle, in a process known as 'DNA methylation'.[114]

A 2013 study published in Nature Neuroscience reported that mice trained to fear the smell of a chemical called acetophenone passed their fear onto at least two generations.[115][116] The science magazine New Scientist commented on the study saying, "While it needs to be corroborated, this finding seems consistent with Lamarckian inheritance. It is, however, based on epigenetics: changes that tweak the action of genes, not the genes themselves. So it fits with natural selection and may yet give Lamarck's name a sheen of respectability."[117]

Guy Barry wrote that Darwin's hypothesis pangenesis coupled with "Lamarckian somatic cell-derived epigenetic modifications" and de novo RNA and DNA mutations can explain the evolution of the human brain.[118]

Lamarckian elements also appear in the hologenome theory of evolution.[119]

The significance of epigenetic inheritance to the evolutionary process is uncertain. Critics assert that epigenetic inheritance modifications are not inherited past two or three generations, so are not a stable basis for evolutionary change.[122][123] According to a recent review in 2015, "there are no reported epigenetic marks transmitted via the male germ line during more than three generations."[122]

The evolutionary biologist T. Ryan Gregory contends that epigenetic inheritance should not be considered Lamarckian. According to Gregory, Lamarck did not claim the environment imposed direct effects on organisms. Instead, Lamarck "argued that the environment created needs to which organisms responded by using some features more and others less, that this resulted in those features being accentuated or attenuated, and that this difference was then inherited by offspring." Gregory has stated that Lamarckian evolution in the context of epigenetics is actually closer to the view held by Darwin rather than by Lamarck.[6]

In a paper titled Weismann Rules! OK? Epigenetics and the Lamarckian Temptation (2007), David Haig writes that research into epigenetic processes does allow a Lamarckian element in evolution but the processes do not challenge the main tenets of the modern evolutionary synthesis as modern Lamarckians have claimed. Haig argued for the primary of DNA and evolution of epigenetic switches by natural selection.[124] Haig has also written there is a "visceral attraction" to Lamarckian evolution from the public and some scientists as it posits the world with a meaning, in which organisms can shape their own evolutionary destiny.[125]

American biologist Jerry Coyne has stated that "lots of studies show us that Lamarckian inheritance doesnt operate" and epigenetic changes are rarely passed on to future generations, thus do not serve as the basis of evolutionary change.[126] Coyne has also written:

Lamarckism is not a heresy, but simply a hypothesis that hasnt held up... If epigenetics in the second sense is so important in evolution, let us have a list of, say, a hundred adaptations of organisms that evolved in this Larmackian way as opposed to the old, boring, neo-Darwinian way involving inherited changes in DNA sequence... I cant think of a single entry for that list.[127]

Thomas Dickens and Qazi Rahman (2012) have written epigenetic mechanisms such as DNA methylation and histone modification are genetically inherited under the control of natural selection and do not challenge the modern synthesis. Dickens and Rahman have taken issue with the claims of Eva Jablonka and Marion J. Lamb on Lamarckian epigenetic processes.[128]

Edith Heard and Robert Martienssen (2014) in a Cell review were not convinced that epigenetics has revived Lamarckism as there is no evidence epigenetic changes are passed on to successive generations in mammals. They concluded the characteristics that are thought to be the result of epigenetic inheritance may be caused by other factors such as behavioral changes, undetected mutations, microbiome alterations or the transmission of metabolites.[129]

In 2015, Khursheed Iqbal and colleagues discovered that although "endocrine disruptors exert direct epigenetic effects in the exposed fetal germ cells, these are corrected by reprogramming events in the next generation." Molecular biologist Emma Whitelaw has cited this study as an example of evidence disputing Lamarckian epigenetic inheritance.[130] Another critic recently argued that bringing back Lamarck in the context of epigenetics is misleading, commenting, "We should remember [Lamarck] for the good he contributed to science, not for things that resemble his theory only superficially. Indeed, thinking of CRISPR and other phenomena as Lamarckian only obscures the simple and elegant way evolution really works."[131]

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Drosophila melanogaster – Wikipedia

Sunday, December 25th, 2016

Drosophila melanogaster is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting with Charles W. Woodworth's proposal of the use of this species as a model organism, D. melanogaster continues to be widely used for biological research in studies of genetics, physiology, microbial pathogenesis, and life history evolution. It is typically used because it is an animal species that is easy to care for, has four pairs of chromosomes, breeds quickly, and lays many eggs.[2]D. melanogaster is a common pest in homes, restaurants, and other occupied places where food is served.[3]

Flies belonging to the family Tephritidae are also called "fruit flies". This can cause confusion, especially in Australia and South Africa, where the Mediterranean fruit fly Ceratitis capitata is an economic pest.

Wildtype fruit flies are yellow-brown, with brick-red eyes and transverse black rings across the abdomen. They exhibit sexual dimorphism: females are about 2.5 millimeters (0.098in) long; males are slightly smaller with darker backs. Males are easily distinguished from females based on colour differences, with a distinct black patch at the abdomen, less noticeable in recently emerged flies (see fig.), and the sexcombs (a row of dark bristles on the tarsus of the first leg). Furthermore, males have a cluster of spiky hairs (claspers) surrounding the reproducing parts used to attach to the female during mating. There are extensive images at FlyBase.[4]

Egg of D. melanogaster

The D. melanogaster lifespan is about 30 days at 29C (84F).

The developmental period for D. melanogaster varies with temperature, as with many ectothermic species. The shortest development time (egg to adult), 7 days, is achieved at 28C (82F).[5][6] Development times increase at higher temperatures (11 days at 30C or 86F) due to heat stress. Under ideal conditions, the development time at 25C (77F) is 8.5 days,[5][6][7] at 18C (64F) it takes 19 days[5][6] and at 12C (54F) it takes over 50 days.[5][6] Under crowded conditions, development time increases,[8] while the emerging flies are smaller.[8][9] Females lay some 400 eggs (embryos), about five at a time, into rotting fruit or other suitable material such as decaying mushrooms and sap fluxes. The eggs, which are about 0.5mm long, hatch after 1215 hours (at 25C or 77F).[5][6] The resulting larvae grow for about 4 days (at 25C) while molting twice (into second- and third-instar larvae), at about 24 and 48 h after hatching.[5][6] During this time, they feed on the microorganisms that decompose the fruit, as well as on the sugar of the fruit itself. The mother puts feces on the egg sacs to establish the same microbial composition in the larvae's guts which has worked positively for herself.[10] Then the larvae encapsulate in the puparium and undergo a four-day-long metamorphosis (at 25C), after which the adults eclose (emerge).[5][6]

Females become receptive to courting males at about 812 hours after emergence.[11] Specific neuron groups in females have been found to affect copulation behavior and mate choice. One such group in the abdominal nerve cord allows the female fly to pause her body movements to copulate.[12] Activation of these neurons induces the female to cease movement and orient herself towards the male to allow for mounting. If the group is inactivated, the female remains in motion and does not copulate. Various chemical signals such as male pheromones often are able to activate the group.[12]

The female fruit fly prefers a shorter duration when it comes to sex. Males, on the other hand, prefer it to last longer.[13] Males perform a sequence of five behavioral patterns to court females. First, males orient themselves while playing a courtship song by horizontally extending and vibrating their wings. Soon after, the male positions itself at the rear of the female's abdomen in a low posture to tap and lick the female genitalia. Finally, the male curls its abdomen and attempts copulation. Females can reject males by moving away, kicking, and extruding their ovipositor.[14] Copulation lasts around 1520 minutes,[15] during which males transfer a few hundred, very long (1.76mm) sperm cells in seminal fluid to the female.[16] Females store the sperm in a tubular receptacle and in two mushroom-shaped spermathecae; sperm from multiple matings compete for fertilization. A last male precedence is believed to exist in which the last male to mate with a female sires about 80% of her offspring. This precedence was found to occur through both displacement and incapacitation.[17] The displacement is attributed to sperm handling by the female fly as multiple matings are conducted and is most significant during the first 12 days after copulation. Displacement from the seminal receptacle is more significant than displacement from the spermathecae.[17] Incapacitation of first male sperm by second male sperm becomes significant 27 days after copulation. The seminal fluid of the second male is believed to be responsible for this incapacitation mechanism (without removal of first male sperm) which takes effect before fertilization occurs.[17] The delay in effectiveness of the incapacitation mechanism is believed to be a protective mechanism that prevents a male fly from incapacitating its own sperm should it mate with the same female fly repetitively. Sensory neurons in the uterus of female D. melanogaster respond to a male protein, sex peptide, which is found in sperm.[12] This protein makes the female reluctant to copulate for about 10 days after insemination. The signal pathway leading to this change in behavior has been determined. The signal is sent to a brain region that is a homolog of the hypothalamus and the hypothalamus then controls sexual behavior and desire[12]

D. melanogaster is often used for life extension studies, such as to identify genes purported to increase lifespan when mutated.[18]

D. melanogaster females exhibit mate choice copying. When virgin females are shown other females copulating with a certain type of male, they tend to copulate more with this type of male afterwards than naive females (which have not observed the copulation of others). This behavior is sensitive to environmental conditions, and females copy less in bad weather conditions.[19]

D. melanogaster males exhibit a strong reproductive learning curve. That is, with sexual experience, these flies tend to modify their future mating behavior in multiple ways. These changes include increased selectivity for courting only intraspecifically, as well as decreased courtship times.

Sexually nave D. melanogaster males are known to spend significant time courting interspecifically, such as with D. simulans flies. Nave D. melanogaster will also attempt to court females that are not yet sexually mature, and other males. D. melanogaster males show little to no preference for D. melanogaster females over females of other species or even other male flies. However, after D. simulans or other flies incapable of copulation have rejected the males advances, D. melanogaster males are much less likely to spend time courting nonspecifically in the future. This apparent learned behavior modification seems to be evolutionarily significant, as it allows the males to avoid investing energy into futile sexual encounters.[20]

In addition, males with previous sexual experience will modify their courtship dance when attempting to mate with new females the experienced males spend less time courting and therefore have lower mating latencies, meaning that they are able to reproduce more quickly. This decreased mating latency leads to a greater mating efficiency for experienced males over nave males.[21] This modification also appears to have obvious evolutionary advantages, as increased mating efficiency is extremely important in the eyes of natural selection.

Both male and female D. melanogaster act polygamously (having multiple sexual partners at the same time).[22] In both males and females, polygamy results in a decrease in evening activity compared to virgin flies, more so in males than females.[22] Evening activity consists of the activities that the flies participate in other than mating and finding partners, such as finding food.[23] The reproductive success of males and females varies, due to the fact that a female only needs to mate once to reach maximum fertility.[23] Mating with multiple partners provides no advantage over mating with one partner, and therefore females exhibit no difference in evening activity between polygamous and monogamous individuals.[23] For males, however, mating with multiple partners increases their reproductive success by increasing the genetic diversity of their offspring.[23] This benefit of genetic diversity is an evolutionary advantage because it increases the chance that some of the offspring will have traits that increase their fitness in their environment.

The difference in evening activity between polygamous and monogamous male flies can be explained with courtship. For polygamous flies, their reproductive success increases by having offspring with multiple partners, and therefore they spend more time and energy on courting multiple females.[23] On the other hand, monogamous flies only court one female, and expend less energy doing so.[23] While it requires more energy for male flies to court multiple females, the overall reproductive benefits it produces has kept polygamy as the preferred sexual choice.[23]

It has been shown that the mechanism that affects courtship behavior in Drosophila is controlled by the oscillator neurons DN1s and LNDs.[24] Oscillation of the DN1 neurons was found to be effected by socio-sexual interactions, and is connected to mating-related decrease of evening activity.[24]

D. melanogaster was among the first organisms used for genetic analysis, and today it is one of the most widely used and genetically best-known of all eukaryotic organisms. All organisms use common genetic systems; therefore, comprehending processes such as transcription and replication in fruit flies helps in understanding these processes in other eukaryotes, including humans.[25]

Thomas Hunt Morgan began using fruit flies in experimental studies of heredity at Columbia University in 1910 in a laboratory known as the Fly Room. The Fly Room was cramped with eight desks, each occupied by students and their experiments. They started off experiments using milk bottles to rear the fruit flies and handheld lenses for observing their traits. The lenses were later replaced by microscopes, which enhanced their observations. Morgan and his students eventually elucidated many basic principles of heredity, including sex-linked inheritance, epistasis, multiple alleles, and gene mapping.[25]

D. melanogaster is one of the most studied organisms in biological research, particularly in genetics and developmental biology. The several reasons include:

Genetic markers are commonly used in Drosophila research, for example within balancer chromosomes or P-element inserts, and most phenotypes are easily identifiable either with the naked eye or under a microscope. In the list of example common markers below, the allele symbol is followed by the name of the gene affected and a description of its phenotype. (Note: Recessive alleles are in lower case, while dominant alleles are capitalised.)

Drosophila genes are traditionally named after the phenotype they cause when mutated. For example, the absence of a particular gene in Drosophila will result in a mutant embryo that does not develop a heart. Scientists have thus called this gene tinman, named after the Oz character of the same name.[27] This system of nomenclature results in a wider range of gene names than in other organisms.

The genome of D. melanogaster (sequenced in 2000, and curated at the FlyBase database[26]) contains four pairs of chromosomes: an X/Y pair, and three autosomes labeled 2, 3, and 4. The fourth chromosome is so tiny, it is often ignored, aside from its important eyeless gene. The D. melanogaster sequenced genome of 139.5 million base pairs has been annotated[28] and contains around 15,682 genes according to Ensemble release 73. More than 60% of the genome appears to be functional non-protein-coding DNA[29] involved in gene expression control. Determination of sex in Drosophila occurs by the X:A ratio of X chromosomes to autosomes, not because of the presence of a Y chromosome as in human sex determination. Although the Y chromosome is entirely heterochromatic, it contains at least 16 genes, many of which are thought to have male-related functions.[30]

A March 2000 study by National Human Genome Research Institute comparing the fruit fly and human genome estimated that about 60% of genes are conserved between the two species.[31] About 75% of known human disease genes have a recognizable match in the genome of fruit flies,[32] and 50% of fly protein sequences have mammalian homologs. An online database called Homophila is available to search for human disease gene homologues in flies and vice versa.[33]Drosophila is being used as a genetic model for several human diseases including the neurodegenerative disorders Parkinson's, Huntington's, spinocerebellar ataxia and Alzheimer's disease. The fly is also being used to study mechanisms underlying aging and oxidative stress, immunity, diabetes, and cancer, as well as drug abuse.

Embryogenesis in Drosophila has been extensively studied, as its small size, short generation time, and large brood size makes it ideal for genetic studies. It is also unique among model organisms in that cleavage occurs in a syncytium.

During oogenesis, cytoplasmic bridges called "ring canals" connect the forming oocyte to nurse cells. Nutrients and developmental control molecules move from the nurse cells into the oocyte. In the figure to the left, the forming oocyte can be seen to be covered by follicular support cells.

After fertilization of the oocyte, the early embryo (or syncytial embryo) undergoes rapid DNA replication and 13 nuclear divisions until about 5000 to 6000 nuclei accumulate in the unseparated cytoplasm of the embryo. By the end of the eighth division, most nuclei have migrated to the surface, surrounding the yolk sac (leaving behind only a few nuclei, which will become the yolk nuclei). After the 10th division, the pole cells form at the posterior end of the embryo, segregating the germ line from the syncytium. Finally, after the 13th division, cell membranes slowly invaginate, dividing the syncytium into individual somatic cells. Once this process is completed, gastrulation starts.[34]

Nuclear division in the early Drosophila embryo happens so quickly, no proper checkpoints exist, so mistakes may be made in division of the DNA. To get around this problem, the nuclei that have made a mistake detach from their centrosomes and fall into the centre of the embryo (yolk sac), which will not form part of the fly.

The gene network (transcriptional and protein interactions) governing the early development of the fruit fly embryo is one of the best understood gene networks to date, especially the patterning along the anteroposterior (AP) and dorsoventral (DV) axes (See under morphogenesis).[34]

The embryo undergoes well-characterized morphogenetic movements during gastrulation and early development, including germ-band extension, formation of several furrows, ventral invagination of the mesoderm, and posterior and anterior invagination of endoderm (gut), as well as extensive body segmentation until finally hatching from the surrounding cuticle into a first-instar larva.

During larval development, tissues known as imaginal discs grow inside the larva. Imaginal discs develop to form most structures of the adult body, such as the head, legs, wings, thorax, and genitalia. Cells of the imaginal disks are set aside during embryogenesis and continue to grow and divide during the larval stagesunlike most other cells of the larva, which have differentiated to perform specialized functions and grow without further cell division. At metamorphosis, the larva forms a pupa, inside which the larval tissues are reabsorbed and the imaginal tissues undergo extensive morphogenetic movements to form adult structures.

Drosophila flies have both X and Y chromosomes, as well as autosomes. Unlike humans, the Y chromosome does not confer maleness; rather, it encodes genes necessary for making sperm. Sex is instead determined by the ratio of X chromosomes to autosomes. Furthermore, each cell "decides" whether to be male or female independently of the rest of the organism, resulting in the occasional occurrence of gynandromorphs.

Three major genes are involved in determination of Drosophila sex. These are sex-lethal, sisterless, and deadpan. Deadpan is an autosomal gene which inhibits sex-lethal, while sisterless is carried on the X chromosome and inhibits the action of deadpan. An AAX cell has twice as much deadpan as sisterless, so sex-lethal will be inhibited, creating a male. However, an AAXX cell will produce enough sisterless to inhibit the action of deadpan, allowing the sex-lethal gene to be transcribed to create a female.

Later, control by deadpan and sisterless disappears and what becomes important is the form of the sex-lethal gene. A secondary promoter causes transcription in both males and females. Analysis of the cDNA has shown that different forms are expressed in males and females. Sex-lethal has been shown to affect the splicing of its own mRNA. In males, the third exon is included which encodes a stop codon, causing a truncated form to be produced. In the female version, the presence of sex-lethal causes this exon to be missed out; the other seven amino acids are produced as a full peptide chain, again giving a difference between males and females.[35]

Presence or absence of functional sex-lethal proteins now go on to affect the transcription of another protein known as doublesex. In the absence of sex-lethal, doublesex will have the fourth exon removed and be translated up to and including exon 6 (DSX-M[ale]), while in its presence the fourth exon which encodes a stop codon will produce a truncated version of the protein (DSX-F[emale]). DSX-F causes transcription of Yolk proteins 1 and 2 in somatic cells, which will be pumped into the oocyte on its production.

Unlike mammals, Drosophila flies only have innate immunity and lack an adaptive immune response. The D. melanogaster immune system can be divided into two responses: humoral and cell-mediated. The former is a systemic response mediated through the Toll and imd pathways, which are parallel systems for detecting microbes. The Toll pathway in Drosophila is known as the homologue of Toll-like pathways in mammals. Spatzle, a known ligand for the Toll pathway in flies, is produced in response to Gram-positive bacteria, parasites, and fungal infection. Upon infection, pro-Spatzle will be cleaved by protease SPE (Spatzle processing enzyme) to become active Spatzle, which then binds to the Toll receptor located on the cell surface (Fat body, hemocytes) and dimerise for activation of downstream NF-B signaling pathways. The imd pathway, though, is triggered by Gram-negative bacteria through soluble and surface receptors (PGRP-LE and LC, respectively). D. melanogaster has a "fat body", which is thought to be homologous to the human liver. It is the primary secretory organ and produces antimicrobial peptides. These peptides are secreted into the hemolymph and bind infectious bacteria, killing them by forming pores in their cell walls. Years ago[when?] many drug companies wanted to purify these peptides and use them as antibiotics. Other than the fat body, hemocytes, the blood cells in Drosophila, are known as the homologue of mammalian monocyte/macrophages, possessing a significant role in immune responses. It is known from the literature that in response to immune challenge, hemocytes are able to secrete cytokines, for example Spatzle, to activate downstream signaling pathways in the fat body. However, the mechanism still remains unclear.

In 1971, Ron Konopka and Seymour Benzer published "Clock mutants of Drosophila melanogaster", a paper describing the first mutations that affected an animal's behavior. Wild-type flies show an activity rhythm with a frequency of about a day (24 hours). They found mutants with faster and slower rhythms, as well as broken rhythmsflies that move and rest in random spurts. Work over the following 30 years has shown that these mutations (and others like them) affect a group of genes and their products that comprise a biochemical or biological clock. This clock is found in a wide range of fly cells, but the clock-bearing cells that control activity are several dozen neurons in the fly's central brain.

Since then, Benzer and others have used behavioral screens to isolate genes involved in vision, olfaction, audition, learning/memory, courtship, pain, and other processes, such as longevity.

The first learning and memory mutants (dunce, rutabaga, etc.) were isolated by William "Chip" Quinn while in Benzer's lab, and were eventually shown to encode components of an intracellular signaling pathway involving cyclic AMP, protein kinase A, and a transcription factor known as CREB. These molecules were shown to be also involved in synaptic plasticity in Aplysia and mammals.[citation needed]

Male flies sing to the females during courtship using their wings to generate sound, and some of the genetics of sexual behavior have been characterized. In particular, the fruitless gene has several different splice forms, and male flies expressing female splice forms have female-like behavior and vice versa. The TRP channels nompC, nanchung, and inactive are expressed in sound-sensitive Johnston's organ neurons and participate in the transduction of sound.[36][37]

Furthermore, Drosophila has been used in neuropharmacological research, including studies of cocaine and alcohol consumption. Models for Parkinson's disease also exist for flies.[38]

Stereo images of the fly eye

The compound eye of the fruit fly contains 760 unit eyes or ommatidia, and are one of the most advanced among insects. Each ommatidium contains eight photoreceptor cells (R1-8), support cells, pigment cells, and a cornea. Wild-type flies have reddish pigment cells, which serve to absorb excess blue light so the fly is not blinded by ambient light.

Each photoreceptor cell consists of two main sections, the cell body and the rhabdomere. The cell body contains the nucleus, while the 100-m-long rhabdomere is made up of toothbrush-like stacks of membrane called microvilli. Each microvillus is 12 m in length and about 60 nm in diameter.[39] The membrane of the rhabdomere is packed with about 100 million rhodopsin molecules, the visual protein that absorbs light. The rest of the visual proteins are also tightly packed into the microvillar space, leaving little room for cytoplasm.

The photoreceptors in Drosophila express a variety of rhodopsin isoforms. The R1-R6 photoreceptor cells express rhodopsin1 (Rh1), which absorbs blue light (480nm). The R7 and R8 cells express a combination of either Rh3 or Rh4, which absorb UV light (345nm and 375nm), and Rh5 or Rh6, which absorb blue (437nm) and green (508nm) light, respectively. Each rhodopsin molecule consists of an opsin protein covalently linked to a carotenoid chromophore, 11-cis-3-hydroxyretinal.[40]

As in vertebrate vision, visual transduction in invertebrates occurs via a G protein-coupled pathway. However, in vertebrates, the G protein is transducin, while the G protein in invertebrates is Gq (dgq in Drosophila). When rhodopsin (Rh) absorbs a photon of light its chromophore, 11-cis-3-hydroxyretinal, is isomerized to all-trans-3-hydroxyretinal. Rh undergoes a conformational change into its active form, metarhodopsin. Metarhodopsin activates Gq, which in turn activates a phospholipase C (PLC) known as NorpA.[41]

PLC hydrolyzes phosphatidylinositol (4,5)-bisphosphate (PIP2), a phospholipid found in the cell membrane, into soluble inositol triphosphate (IP3) and diacylglycerol (DAG), which stays in the cell membrane. DAG or a derivative of DAG causes a calcium-selective ion channel known as transient receptor potential (TRP) to open and calcium and sodium flows into the cell. IP3 is thought to bind to IP3 receptors in the subrhabdomeric cisternae, an extension of the endoplasmic reticulum, and cause release of calcium, but this process does not seem to be essential for normal vision.[41]

Calcium binds to proteins such as calmodulin (CaM) and an eye-specific protein kinase C (PKC) known as InaC. These proteins interact with other proteins and have been shown to be necessary for shut off of the light response. In addition, proteins called arrestins bind metarhodopsin and prevent it from activating more Gq. A sodium-calcium exchanger known as CalX pumps the calcium out of the cell. It uses the inward sodium gradient to export calcium at a stoichiometry of 3 Na+/ 1 Ca++.[42]

TRP, InaC, and PLC form a signaling complex by binding a scaffolding protein called InaD. InaD contains five binding domains called PDZ domain proteins, which specifically bind the C termini of target proteins. Disruption of the complex by mutations in either the PDZ domains or the target proteins reduces the efficiency of signaling. For example, disruption of the interaction between InaC, the protein kinase C, and InaD results in a delay in inactivation of the light response.

Unlike vertebrate metarhodopsin, invertebrate metarhodopsin can be converted back into rhodopsin by absorbing a photon of orange light (580nm).

About two-thirds of the Drosophila brain is dedicated to visual processing.[43] Although the spatial resolution of their vision is significantly worse than that of humans, their temporal resolution is around 10 times better.

The wings of a fly are capable of beating up to 220 times per second.[citation needed] Flies fly via straight sequences of movement interspersed by rapid turns called saccades.[44] During these turns, a fly is able to rotate 90 in less than 50 milliseconds.[44]

Characteristics of Drosophila flight may be dominated by the viscosity of the air, rather than the inertia of the fly body, but the opposite case with inertia as the dominant force may occur.[44] However, subsequent work showed that while the viscous effects on the insect body during flight may be negligible, the aerodynamic forces on the wings themselves actually cause fruit flies' turns to be damped viscously.[45]

Drosophila is commonly considered a pest due to its tendency to infest habitations and establishments where fruit is found; the flies may collect in homes, restaurants, stores, and other locations.[3] Removal of an infestation can be difficult, as larvae may continue to hatch in nearby fruit even as the adult population is eliminated.

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Ageing – Wikipedia

Wednesday, December 7th, 2016

Ageing, also spelled aging, is the process of becoming older. The term refers especially to human beings, many animals, and fungi, whereas for example bacteria, perennial plants and some simple animals are potentially immortal. In the broader sense, ageing can refer to single cells within an organism which have ceased dividing (cellular senescence) or to the population of a species (population ageing).

In humans, ageing represents the accumulation of changes in a human being over time,[1] encompassing physical, psychological, and social change. Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand. Ageing is among the greatest known risk factors for most human diseases:[2] of the roughly 150,000 people who die each day across the globe, about two thirds die from age-related causes.

The causes of ageing are unknown; current theories are assigned to the damage concept, whereby the accumulation of damage (such as DNA breaks, oxidised DNA and/or mitochondrial malfunctions)[3] may cause biological systems to fail, or to the programmed ageing concept, whereby internal processes (such as DNA telomere shortening) may cause ageing. Programmed ageing should not be confused with programmed cell death (apoptosis).

The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats has motivated research into delaying and preventing ageing.

Human beings and members of other species, especially animals, necessarily experience ageing and mortality. Fungi, too, can age.[4] In contrast, many species can be considered immortal: for example, bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, and animals in the genus Hydra have a regenerative ability with which they avoid dying of old age.

Early life forms on Earth, starting at least 3.7 billion years ago,[5] were single-celled organisms. Such single-celled organisms (prokaryotes, protozoans, algae) multiply by fissioning into daughter cells, thus do not age and are innately immortal.[6][7]

Ageing and mortality of the individual organism became possible with the evolution of sexual reproduction,[8] which occurred with the emergence of the fungal/animal kingdoms approximately a billion years ago, and with the evolution of flowering plants 160 million years ago. The sexual organism could henceforth pass on some of its genetic material to produce new individuals and itself could become disposable with regards to the survival of its species.[8] This classic biological idea has however been perturbed recently by the discovery that the bacterium E. coli may split into distinguishable daughter cells, which opens the theoretical possibility of "age classes" among bacteria.[9]

Even within humans and other mortal species, there are cells with the potential for immortality: cancer cells which have lost the ability to die when maintained in cell culture such as the HeLa cell line,[10] and specific stem cells such as germ cells (producing ova and spermatozoa).[11] In artificial cloning, adult cells can be rejuvenated back to embryonic status and then used to grow a new tissue or animal without ageing.[12] Normal human cells however die after about 50 cell divisions in laboratory culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961).[10]

A number of characteristic ageing symptoms are experienced by a majority or by a significant proportion of humans during their lifetimes.

Dementia becomes more common with age.[35] About 3% of people between the ages of 6574 have dementia, 19% between 75 and 84 and nearly half of those over 85 years of age.[36] The spectrum includes mild cognitive impairment and the neurodegenerative diseases of Alzheimer's disease, cerebrovascular disease, Parkinson's disease and Lou Gehrig's disease. Furthermore, many types of memory may decline with ageing, but not semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady until late adulthood[37] (see Ageing brain). Intelligence may decline with age, though the rate may vary depending on the type and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. Individual variations in rate of cognitive decline may therefore be explained in terms of people having different lengths of life.[38] There might be changes to the brain: after 20 years of age there may be a 10% reduction each decade in the total length of the brain's myelinated axons.[39][40]

Age can result in visual impairment, whereby non-verbal communication is reduced,[41] which can lead to isolation and possible depression. Macular degeneration causes vision loss and increases with age, affecting nearly 12% of those above the age of 80.[42] This degeneration is caused by systemic changes in the circulation of waste products and by growth of abnormal vessels around the retina.[43]

A distinction can be made between "proximal ageing" (age-based effects that come about because of factors in the recent past) and "distal ageing" (age-based differences that can be traced back to a cause early in person's life, such as childhood poliomyelitis).[38]

Ageing is among the greatest known risk factors for most human diseases.[2] Of the roughly 150,000 people who die each day across the globe, about two thirds100,000 per daydie from age-related causes. In industrialised nations, the proportion is higher, reaching 90%.[44][45][46]

At present, researchers are only just beginning to understand the biological basis of ageing even in relatively simple and short-lived organisms such as yeast.[47] Less still is known about mammalian ageing, in part due to the much longer lives in even small mammals such as the mouse (around 3 years). A primary model organism for studying ageing is the nematode C. elegans, thanks to its short lifespan of 23 weeks, the ability to easily perform genetic manipulations or suppress gene activity with RNA interference, and other factors.[48] Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans.[49]

Factors that are proposed to influence biological ageing[50] fall into two main categories, programmed and damage-related. Programmed factors follow a biological timetable, perhaps a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defence responses. Damage-related factors include internal and environmental assaults to living organisms that induce cumulative damage at various levels.[51]

There are three main metabolic pathways which can influence the rate of ageing:

It is likely that most of these pathways affect ageing separately, because targeting them simultaneously leads to additive increases in lifespan.[53]

The rate of ageing varies substantially across different species, and this, to a large extent, is genetically based. For example, numerous perennial plants ranging from strawberries and potatoes to willow trees typically produce clones of themselves by vegetative reproduction and are thus potentially immortal, while annual plants such as wheat and watermelons die each year and reproduce by sexual reproduction. In 2008 it was discovered that inactivation of only two genes in the annual plant Arabidopsis thaliana leads to its conversion into a potentially immortal perennial plant.[54]

Clonal immortality apart, there are certain species whose individual lifespans stand out among Earth's life-forms, including the bristlecone pine at 5062 years[55] (however Hayflick states that the bristlecone pine has no cells older than 30 years), invertebrates like the hard clam (known as quahog in New England) at 508 years,[56] the Greenland shark at 400 years,[57] fish like the sturgeon and the rockfish, and the sea anemone[58] and lobster.[59][60] Such organisms are sometimes said to exhibit negligible senescence.[61] The genetic aspect has also been demonstrated in studies of human centenarians.

In laboratory settings, researchers have demonstrated that selected alterations in specific genes can extend lifespan quite substantially in yeast and roundworms, less so in fruit flies and less again in mice. Some of the targeted genes have homologues across species and in some cases have been associated with human longevity.[62]

Caloric restriction substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases.[103] Typically, this involves caloric intake of 6070% of what an ad libitum animal would consume, while still maintaining proper nutrient intake.[103] In rodents, this has been shown to increase lifespan by up to 50%;[104] similar effects occur for yeast and Drosophila.[103] No lifespan data exist for humans on a calorie-restricted diet,[76] but several reports support protection from age-related diseases.[105][106] Two major ongoing studies on rhesus monkeys initially revealed disparate results; while one study, by the University of Wisconsin, showed that caloric restriction does extend lifespan,[107] the second study, by the National Institute on Ageing (NIA), found no effects of caloric restriction on longevity.[108] Both studies nevertheless showed improvement in a number of health parameters. Notwithstanding the similarly low calorie intake, the diet composition differed between the two studies (notably a high sucrose content in the Wisconsin study), and the monkeys have different origins (India, China), initially suggesting that genetics and dietary composition, not merely a decrease in calories, are factors in longevity.[76] However, in a comparative analysis in 2014, the Wisconsin researchers found that the allegedly non-starved NIA control monkeys in fact are moderately underweight when compared with other monkey populations, and argued this was due to the NIA's apportioned feeding protocol in contrast to Wisconsin's truly unrestricted ad libitum feeding protocol.[109] They conclude that moderate calorie restriction rather than extreme calorie restriction is sufficient to produce the observed health and longevity benefits in the studied rhesus monkeys.[110]

In his book How and Why We Age, Hayflick says that caloric restriction may not be effective in humans, citing data from the Baltimore Longitudinal Study of Aging which shows that being thin does not favour longevity.[need quotation to verify][111] Similarly, it is sometimes claimed that moderate obesity in later life may improve survival, but newer research has identified confounding factors such as weight loss due to terminal disease. Once these factors are accounted for, the optimal body weight above age 65 corresponds to a leaner body mass index of 23 to 27.[112]

Alternatively, the benefits of dietary restriction can also be found by changing the macro nutrient profile to reduce protein intake without any changes to calorie level, resulting in similar increases in longevity.[113][114] Dietary protein restriction not only inhibits mTOR activity but also IGF-1, two mechanisms implicated in ageing.[74] Specifically, reducing leucine intake is sufficient to inhibit mTOR activity, achievable through reducing animal food consumption.[115][116]

The Mediterranean diet is credited with lowering the risk of heart disease and early death.[117][118] The major contributors to mortality risk reduction appear to be a higher consumption of vegetables, fish, fruits, nuts and monounsaturated fatty acids, i.e., olive oil.[119]

The amount of sleep has an impact on mortality. People who live the longest report sleeping for six to seven hours each night.[120][121] Lack of sleep (<5 hours) more than doubles the risk of death from cardiovascular disease, but too much sleep (>9 hours) is associated with a doubling of the risk of death, though not primarily from cardiovascular disease.[122] Sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality, though the cause is probably other factors such as depression and socioeconomic status, which would correlate statistically.[123] Sleep monitoring of hunter-gatherer tribes from Africa and from South America has shown similar sleep patterns across continents: their average sleeping duration is 6.4 hours (with a summer/winter difference of 1 hour), afternoon naps (siestas) are uncommon, and insomnia is very rare (tenfold less than in industrial societies).[124]

Physical exercise may increase life expectancy.[125] People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active.[126] Moderate levels of exercise have been correlated with preventing aging and improving quality of life by reducing inflammatory potential.[127] The majority of the benefits from exercise are achieved with around 3500 metabolic equivalent (MET) minutes per week.[128] For example, climbing stairs 10 minutes, vacuuming 15 minutes, gardening 20 minutes, running 20 minutes, and walking or bicycling for 25 minutes on a daily basis would together achieve about 3000 MET minutes a week.[128]

Avoidance of chronic stress (as opposed to acute stress) is associated with a slower loss of telomeres in most but not all studies,[129][130] and with decreased cortisol levels. A chronically high cortisol level compromises the immune system, causes cardiac damage/arterosclerosis and is associated with facial ageing, and the latter in turn is a marker for increased morbidity and mortality.[131][132] Stress can be countered by social connection, spirituality, and (for men more clearly than for women) married life, all of which are associated with longevity.[133][134][135]

The following drugs and interventions have been shown to retard or reverse the biological effects of ageing in animal models, but none has yet been proven to do so in humans.

Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.[136]

As of 2015 metformin was under study for its potential effect on slowing ageing in the worm C.elegans and the cricket.[137] Its effect on otherwise healthy humans is unknown.[137]

Rapamycin was first shown to extend lifespan in eukaryotes in 2006 by Powers et al. who showed a dose-responsive effect of rapamycin on lifespan extension in yeast cells.[138] In a 2009 study, the lifespans of mice fed rapamycin were increased between 28 and 38% from the beginning of treatment, or 9 to 14% in total increased maximum lifespan. Of particular note, the treatment began in mice aged 20 months, the equivalent of 60 human years.[139] Rapamycin has subsequently been shown to extend mouse lifespan in several separate experiments,[140][141] and is now being tested for this purpose in nonhuman primates (the marmoset monkey).[142]

Cancer geneticist Ronald A. DePinho and his colleagues published research in mice where telomerase activity was first genetically removed. Then, after the mice had prematurely aged, they restored telomerase activity by reactivating the telomerase gene. As a result, the mice were rejuvenated: Shrivelled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver, intestines and brain, recuperated from their degenerated state. "[The finding] offers the possibility that normal human ageing could be slowed by reawakening the enzyme in cells where it has stopped working" says Ronald DePinho. However, activating telomerase in humans could potentially encourage the growth of tumours.[143]

Most known genetic interventions in C. elegans increase lifespan by 1.5 to 2.5-fold. As of 2009[update], the record for lifespan extension in C. elegans is a single-gene mutation which increases adult survival by tenfold.[49] The strong conservation of some of the mechanisms of ageing discovered in model organisms imply that they may be useful in the enhancement of human survival. However, the benefits may not be proportional; longevity gains are typically greater in C. elegans than fruit flies, and greater in fruit flies than in mammals. One explanation for this is that mammals, being much longer-lived, already have many traits which promote lifespan.[49]

Some research effort is directed to slow ageing and extend healthy lifespan.[144][145][146]

The US National Institute on Aging currently funds an intervention testing programme, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice.[147] Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals and lax mouse husbandry conditions.[citation needed] The intervention testing programme aims to address this by conducting parallel experiments at three internationally recognised mouse ageing-centres, the Barshop Institute at UTHSCSA, the University of Michigan at Ann Arbor and the Jackson Laboratory.

Several companies and organisations, such as Google Calico, Human Longevity, Craig Venter, Gero,[148]SENS Research Foundation, and Science for Life Extension in Russia,[149] declared stopping or delaying ageing as their goal.

Prizes for extending lifespan and slowing ageing in mammals exist. The Methuselah Foundation offers the Mprize. Recently, the $1 Million Palo Alto Longevity Prize was launched. It is a research incentive prize to encourage teams from all over the world to compete in an all-out effort to "hack the code" that regulates our health and lifespan. It was founded by Joon Yun.[150][151][152][153][154]

Different cultures express age in different ways. The age of an adult human is commonly measured in whole years since the day of birth. Arbitrary divisions set to mark periods of life may include: juvenile (via infancy, childhood, preadolescence, adolescence), early adulthood, middle adulthood, and late adulthood. More casual terms may include "teenagers," "tweens," "twentysomething", "thirtysomething", etc. as well as "vicenarian", "tricenarian", "quadragenarian", etc.

Most legal systems define a specific age for when an individual is allowed or obliged to do particular activities. These age specifications include voting age, drinking age, age of consent, age of majority, age of criminal responsibility, marriageable age, age of candidacy, and mandatory retirement age. Admission to a movie for instance, may depend on age according to a motion picture rating system. A bus fare might be discounted for the young or old. Each nation, government and non-governmental organisation has different ways of classifying age. In other words, chronological ageing may be distinguished from "social ageing" (cultural age-expectations of how people should act as they grow older) and "biological ageing" (an organism's physical state as it ages).[155]

In a UNFPA report about ageing in the 21st century, it highlighted the need to "Develop a new rights-based culture of ageing and a change of mindset and societal attitudes towards ageing and older persons, from welfare recipients to active, contributing members of society."[156] UNFPA said that this "requires, among others, working towards the development of international human rights instruments and their translation into national laws and regulations and affirmative measures that challenge age discrimination and recognise older people as autonomous subjects."[156] Older persons make contributions to society including caregiving and volunteering. For example, "A study of Bolivian migrants who [had] moved to Spain found that 69% left their children at home, usually with grandparents. In rural China, grandparents care for 38% of children aged under five whose parents have gone to work in cities."[156]

Population ageing is the increase in the number and proportion of older people in society. Population ageing has three possible causes: migration, longer life expectancy (decreased death rate) and decreased birth rate. Ageing has a significant impact on society. Young people tend to have fewer legal privileges (if they are below the age of majority), they are more likely to push for political and social change, to develop and adopt new technologies, and to need education. Older people have different requirements from society and government, and frequently have differing values as well, such as for property and pension rights.[157]

In the 21st century, one of the most significant population trends is ageing.[158] Currently, over 11% of the world's current population are people aged 60 and older and the United Nations Population Fund (UNFPA) estimates that by 2050 that number will rise to approximately 22%.[156] Ageing has occurred due to development which has enabled better nutrition, sanitation, health care, education and economic well-being. Consequently, fertility rates have continued to decline and life expectancy have risen. Life expectancy at birth is over 80 now in 33 countries. Ageing is a "global phenomenon," that is occurring fastest in developing countries, including those with large youth populations, and poses social and economic challenges to the work which can be overcome with "the right set of policies to equip individuals, families and societies to address these challenges and to reap its benefits."[159]

As life expectancy rises and birth rates decline in developed countries, the median age rises accordingly. According to the United Nations, this process is taking place in nearly every country in the world.[160] A rising median age can have significant social and economic implications, as the workforce gets progressively older and the number of old workers and retirees grows relative to the number of young workers. Older people generally incur more health-related costs than do younger people in the workplace and can also cost more in worker's compensation and pension liabilities.[161] In most developed countries an older workforce is somewhat inevitable. In the United States for instance, the Bureau of Labor Statistics estimates that one in four American workers will be 55 or older by 2020.[161]

Among the most urgent concerns of older persons worldwide is income security. This poses challenges for governments with ageing populations to ensure investments in pension systems continues in order to provide economic independence and reduce poverty in old age. These challenges vary for developing and developed countries. UNFPA stated that, "Sustainability of these systems is of particular concern, particularly in developed countries, while social protection and old-age pension coverage remain a challenge for developing countries, where a large proportion of the labour force is found in the informal sector."[156]

The global economic crisis has increased financial pressure to ensure economic security and access to health care in old age. In order to elevate this pressure "social protection floors must be implemented in order to guarantee income security and access to essential health and social services for all older persons and provide a safety net that contributes to the postponement of disability and prevention of impoverishment in old age."[156]

It has been argued that population ageing has undermined economic development.[162] Evidence suggests that pensions, while making a difference to the well-being of older persons, also benefit entire families especially in times of crisis when there may be a shortage or loss of employment within households. A study by the Australian Government in 2003 estimated that "women between the ages of 65 and 74 years contribute A$16 billion per year in unpaid caregiving and voluntary work. Similarly, men in the same age group contributed A$10 billion per year."[156]

Due to increasing share of the elderly in the population, health care expenditures will continue to grow relative to the economy in coming decades. This has been considered as a negative phenomenon and effective strategies like labour productivity enhancement should be considered to deal with negative consequences of ageing.[163]

In the field of sociology and mental health, ageing is seen in five different views: ageing as maturity, ageing as decline, ageing as a life-cycle event, ageing as generation, and ageing as survival.[164] Positive correlates with ageing often include economics, employment, marriage, children, education, and sense of control, as well as many others. The social science of ageing includes disengagement theory, activity theory, selectivity theory, and continuity theory. Retirement, a common transition faced by the elderly, may have both positive and negative consequences.[165] As cyborgs currently are on the rise some theorists argue there is a need to develop new definitions of ageing and for instance a bio-techno-social definition of ageing has been suggested.[166]

With age inevitable biological changes occur that increase the risk of illness and disability. UNFPA states that,[159]

"A life-cycle approach to health care one that starts early, continues through the reproductive years and lasts into old age is essential for the physical and emotional well-being of older persons, and, indeed, all people. Public policies and programmes should additionally address the needs of older impoverished people who cannot afford health care."

Many societies in Western Europe and Japan have ageing populations. While the effects on society are complex, there is a concern about the impact on health care demand. The large number of suggestions in the literature for specific interventions to cope with the expected increase in demand for long-term care in ageing societies can be organised under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters.[167]

However, the annual growth in national health spending is not mainly due to increasing demand from ageing populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients.[168] A number of health problems become more prevalent as people get older. These include mental health problems as well as physical health problems, especially dementia.

It has been estimated that population ageing only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3% since 1970. In addition, certain reforms to the Medicare system in the United States decreased elderly spending on home health care by 12.5% per year between 1996 and 2000.[169]

Positive self-perception of health has been correlated with higher well-being and reduced mortality in the elderly.[170][171] Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better than that of their ill counterparts, though this link has been observed even in studies which have controlled for socioeconomic status, psychological functioning and health status.[172] This finding is generally stronger for men than women,[171] though this relationship is not universal across all studies and may only be true in some circumstances.[172]

As people age, subjective health remains relatively stable, even though objective health worsens.[173] In fact, perceived health improves with age when objective health is controlled in the equation.[174] This phenomenon is known as the "paradox of ageing." This may be a result of social comparison;[175] for instance, the older people get, the more they may consider themselves in better health than their same-aged peers.[176] Elderly people often associate their functional and physical decline with the normal ageing process.[177][178]

The concept of successful ageing can be traced back to the 1950s and was popularised in the 1980s. Traditional definitions of successful ageing have emphasised absence of physical and cognitive disabilities.[179] In their 1987 article, Rowe and Kahn characterised successful ageing as involving three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement.[180]

The ancient Greek dramatist Euripides (5th century BC) describes the multiply-headed mythological monster Hydra as having a regenerative capacity which makes it immortal, which is the historical background to the name of the biological genus Hydra. The Book of Job (c. 6th century BC) describes human lifespan as inherently limited and makes a comparison with the innate immortality that a felled tree may have when undergoing vegetative regeneration.[181]

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Ashkenazi Jews – Wikipedia

Wednesday, December 7th, 2016

Ashkenazi Jews ( Y'hudey Ashkenaz in Ashkenazi Hebrew) Total population (10[1]11.2[2] million) Regions with significant populations United States 56 million[3] Israel 2.8 million[1][4] Russia 194,000500,000 Argentina 300,000 United Kingdom 260,000 Canada 240,000 France 200,000 Germany 200,000 Ukraine 150,000 Australia 120,000 South Africa 80,000 Belarus 80,000 Hungary 75,000 Chile 70,000 Belgium 30,000 Brazil 30,000 Netherlands 30,000 Moldova 30,000 Poland 25,000 Mexico 18,500 Sweden 18,000 Latvia 10,000 Romania 10,000 Austria 9,000 New Zealand 5,000 Azerbaijan 4,300 Lithuania 4,000 Czech Republic 3,000 Slovakia 3,000 Estonia 1,000 Languages Historical: Yiddish Modern: Local languages, primarily:English, Hebrew, Russian Religion Judaism, some secular, irreligious Related ethnic groups Sephardi Jews, Mizrahi Jews, Samaritans,[5][5][6][7]Kurds,[7] other Levantines (Druze, Assyrians,[5][6]Arabs[5][6][8][9]), Mediterranean groups[10][11][12][13][14]

Ashkenazi Jews, also known as Ashkenazic Jews or simply Ashkenazim (Hebrew: , Ashkenazi Hebrew pronunciation: [aknazim], singular: [aknazi], Modern Hebrew: [akenazim, akenazi]; also Y'hudey Ashkenaz),[15] are a Jewish diaspora population who coalesced as a distinct community in the Holy Roman Empire around the end of the first millennium.[16] The traditional diaspora language of Ashkenazi Jews is Yiddish (which incorporates several dialects), while until recently Hebrew was only used as a sacred language.

The Ashkenazim settled and established communities throughout Central and Eastern Europe, which was their primary region of concentration and residence from the Middle Ages until recent times. They subsequently evolved their own distinctive culture and diasporic identities.[17] Throughout their time in Europe, the Ashkenazim have made many important contributions to philosophy, scholarship, literature, art, music and science.[18][19][20][21]

In the late Middle Ages, the center of gravity of the Ashkenazi population shifted steadily eastward,[22] moving out of the Holy Roman Empire into the Pale of Settlement (comprising parts of present-day Belarus, Latvia, Lithuania, Moldova, Poland, Russia, and Ukraine).[23][24] In the course of the late 18th and 19th centuries, those Jews who remained in or returned to the German lands experienced a cultural reorientation; under the influence of the Haskalah and the struggle for emancipation, as well the intellectual and cultural ferment in urban centers, they gradually abandoned the use of Yiddish, while developing new forms of Jewish religious life and cultural identity.[25]

The genocidal impact of the Holocaust (the mass murder of approximately six million Jews during World War II) devastated the Ashkenazim and their culture, affecting almost every Jewish family.[26][27] It is estimated that in the 11th century Ashkenazi Jews composed only three percent of the world's Jewish population, while at their peak in 1931 they accounted for 92 percent of the world's Jews. Immediately prior to the Holocaust, the number of Jews in the world stood at approximately 16.7 million.[28] Statistical figures vary for the contemporary demography of Ashkenazi Jews, oscillating between 10 million[1] and 11.2 million.[2]Sergio DellaPergola in a rough calculation of Sephardic and Mizrahi Jews, implies that Ashkenazi make up less than 74% of Jews worldwide.[29] Other estimates place Ashkenazi Jews as making up about 75% of Jews worldwide.[30]

Genetic studies on Ashkenazimresearching both their paternal and maternal lineagessuggest a significant proportion of West Asian ancestry. Those studies have arrived at diverging conclusions regarding both the degree and the sources of their European ancestry, and have generally focused on the extent of the European genetic origin observed in Ashkenazi maternal lineages.[31] Ashkenazi Jews are popularly contrasted with Sephardi Jews (also called Sephardim), who are descendants of Jews from the Iberian Peninsula (though there are other groups as well). There are some differences in how the two groups pronounce certain Hebrew letters and in points of ritual.

The name Ashkenazi derives from the biblical figure of Ashkenaz, the first son of Gomer, son of Khaphet, son of Noah, and a Japhetic patriarch in the Table of Nations (Genesis 10). The name of Gomer has often been linked to the ethnonym Cimmerians. Biblical Ashkenaz is usually derived from Assyrian Akza (cuneiform Akuzai/Ikuzai), a people who expelled the Cimmerians from the Armenian area of the Upper Euphrates,[32] whose name is usually associated with the name of the Scythians.[33][34] The intrusive n in the Biblical name is likely due to a scribal error confusing a waw with a nun .[34][35][36]

In Jeremiah 51:27, Ashkenaz figures as one of three kingdoms in the far north, the others being Minni and Ararat, perhaps corresponding to Urartu, called on by God to resist Babylon.[36][37]

In the Yoma tractate of the Babylonian Talmud the name Gomer is rendered as Germania, which elsewhere in rabbinical literature was identified with Germanikia in northwestern Syria, but later became associated with Germania. Ashkenaz is linked to Scandza/Scanzia, viewed as the cradle of Germanic tribes, as early as a 6th-century gloss to the Historia Ecclesiastica of Eusebius.[38] In the 10th-century History of Armenia of Yovhannes Drasxanakertc'i (1.15) Ashkenaz was associated with Armenia,[39] as it was occasionally in Jewish usage, where its denotation extended at times to Adiabene, Khazaria, Crimea and areas to the east.[40] His contemporary Saadia Gaon identified Ashkenaz with the Saquliba or Slavic territories,[41] and such usage covered also the lands of tribes neighboring the Slavs, and Eastern and Central Europe.[40] In modern times, Samuel Krauss identified the Biblical "Ashkenaz" with Khazaria.[42]

Sometime in the early medieval period, the Jews of central and eastern Europe came to be called by this term.[36] In conformity with the custom of designating areas of Jewish settlement with biblical names, Spain was denominated Sefarad (Obadiah 20), France was called Tsarefat (1 Kings 17:9), and Bohemia was called the Land of Canaan.[43] By the high medieval period, Talmudic commentators like Rashi began to use Ashkenaz/Eretz Ashkenaz to designate Germany, earlier known as Loter,[36][38] where, especially in the Rhineland communities of Speyer, Worms and Mainz, the most important Jewish communities arose.[44] Rashi uses leshon Ashkenaz (Ashkenazi language) to describe German speech, and Byzantium and Syrian Jewish letters referred to the Crusaders as Ashkenazim.[38] Given the close links between the Jewish communities of France and Germany following the Carolingian unification, the term Ashkenazi came to refer to both the Jews of medieval Germany and France.[45]

Outside of their origins in ancient Israel, the history of Ashkenazim is shrouded in mystery,[46] and many theories have arisen speculating on their emergence as a distinct community of Jews.[47] The most well supported theory is the one that details a Jewish migration from Israel through what is now Italy and other parts of southern Europe.[48] The historical record attests to Jewish communities in southern Europe since pre-Christian times.[49] Many Jews were denied full Roman citizenship until 212 CE, when Emperor Caracalla granted all free peoples this privilege. Jews were required to pay a poll tax until the reign of Emperor Julian in 363. In the late Roman Empire, Jews were free to form networks of cultural and religious ties and enter into various local occupations. But, after Christianity became the official religion of Rome and Constantinople in 380, Jews were increasingly marginalized.

The history of Jews in Greece goes back to at least the Archaic Era of Greece, when the classical culture of Greece was undergoing a process of formalization after the Greek Dark Age. The Greek historian Herodotus knew of the Jews, whom he called "Palestinian Syrians",[citation needed] and listed them among the levied naval forces in service of the invading Persians. While Jewish monotheism was not deeply affected by Greek Polytheism, the Greek way of living was attractive for many wealthier Jews.[50] The Synagogue in the Agora of Athens is dated to the period between 267 and 396 CE. The Stobi Synagogue in Macedonia, was built on the ruins of a more ancient synagogue in the 4th century, while later in the 5th century, the synagogue was transformed into Christian basilica.[51]Hellenistic Judaism thrived in Antioch and Alexandria, many of these Greek-speaking Jews would convert to Christianity.[52] Sporadic[53]epigraphic evidence in grave site excavations, particularly in Brigetio (Szny), Aquincum (buda), Intercisa (Dunajvros), Triccinae (Srvr), Savaria (Szombathely), Sopianae (Pcs) in Hungary, and Osijek in Croatia, attest to the presence of Jews after the 2nd and 3rd centuries where Roman garrisons were established,[54] There was a sufficient number of Jews in Pannonia to form communities and build a synagogue. Jewish troops were among the Syrian soldiers transferred there, and replenished from the Middle East, after 175 C.E. Jews and especially Syrians came from Antioch, Tarsus and Cappadocia. Others came from Italy and the Hellenized parts of the Roman empire. The excavations suggest they first lived in isolated enclaves attached to Roman legion camps, and intermarried among other similar oriental families within the military orders of the region.[53]Raphael Patai states that later Roman writers remarked that they differed little in either customs, manner of writing, or names from the people among whom they dwelt; and it was especially difficult to differentiate Jews from the Syrians.[55][56] After Pannonia was ceded to the Huns in 433, the garrison populations were withdrawn to Italy, and only a few, enigmatic traces remain of a possible Jewish presence in the area some centuries later.[57]

No evidence has yet been found of a Jewish presence in antiquity in Germany beyond its Roman border, nor in Eastern Europe. In Gaul and Germany itself, with the possible exception of Trier and Cologne, the archeological evidence suggests at most a fleeting presence of very few Jews, primarily itinerant traders or artisans.[58] A substantial Jewish population emerged in northern Gaul by the Middle Ages,[59] but Jewish communities existed in 465 CE in Brittany, in 524 CE in Valence, and in 533 CE in Orleans.[60] Throughout this period and into the early Middle Ages, some Jews assimilated into the dominant Greek and Latin cultures, mostly through conversion to Christianity.[61][bettersourceneeded] King Dagobert I of the Franks expelled the Jews from his Merovingian kingdom in 629. Jews in former Roman territories faced new challenges as harsher anti-Jewish Church rulings were enforced.

Charlemagne's expansion of the Frankish empire around 800, including northern Italy and Rome, brought on a brief period of stability and unity in Francia. This created opportunities for Jewish merchants to settle again north of the Alps. Charlemagne granted the Jews freedoms similar to those once enjoyed under the Roman Empire. In addition, Jews from southern Italy, fleeing religious persecution, began to move into central Europe.[citation needed] Returning to Frankish lands, many Jewish merchants took up occupations in finance and commerce, including money lending, or usury. (Church legislation banned Christians from lending money in exchange for interest.) From Charlemagne's time to the present, Jewish life in northern Europe is well documented. By the 11th century, when Rashi of Troyes wrote his commentaries, Jews in what came to be known as "Ashkenaz" were known for their halakhic learning, and Talmudic studies. They were criticized by Sephardim and other Jewish scholars in Islamic lands for their lack of expertise in Jewish jurisprudence (dinim) and general ignorance of Hebrew linguistics and literature.[62]Yiddish emerged as a result of Judeo-Latin language contact with various High German vernaculars in the medieval period.[63] It is a Germanic language written with Hebrew letters, and heavily influenced by Hebrew and Aramaic, with some elements of Romance and later Slavic languages.[64]

Historical records show evidence of Jewish communities north of the Alps and Pyrenees as early as the 8th and 9th century. By the 11th century Jewish settlers, moving from southern European and Middle Eastern centers, appear to have begun to settle in the north, especially along the Rhine, often in response to new economic opportunities and at the invitation of local Christian rulers. Thus Baldwin V, Count of Flanders, invited Jacob ben Yekutiel and his fellow Jews to settle in his lands; and soon after the Norman Conquest of England, William the Conqueror likewise extended a welcome to continental Jews to take up residence there. Bishop Rdiger Huzmann called on the Jews of Mainz to relocate to Speyer. In all of these decisions, the idea that Jews had the know-how and capacity to jump-start the economy, improve revenues, and enlarge trade seems to have played a prominent role.[65] Typically Jews relocated close to the markets and churches in town centres, where, though they came under the authority of both royal and ecclesiastical powers, they were accorded administrative autonomy.[65]

In the 11th century, both Rabbinic Judaism and the culture of the Babylonian Talmud that underlies it became established in southern Italy and then spread north to Ashkenaz.[66]

The Jewish communities along the Rhine river from Cologne to Mainz were decimated in the Rhineland massacres of 1096. With the onset of the Crusades in 1095, and the expulsions from England (1290), France (1394), and parts of Germany (15th century), Jewish migration pushed eastward into Poland (10th century), Lithuania (10th century), and Russia (12th century). Over this period of several hundred years, some have suggested, Jewish economic activity was focused on trade, business management, and financial services, due to several presumed factors: Christian European prohibitions restricting certain activities by Jews, preventing certain financial activities (such as "usurious" loans)[67] between Christians, high rates of literacy, near universal male education, and ability of merchants to rely upon and trust family members living in different regions and countries.

By the 15th century, the Ashkenazi Jewish communities in Poland were the largest Jewish communities of the Diaspora.[68] This area, which eventually fell under the domination of Russia, Austria, and Prussia (Germany), would remain the main center of Ashkenazi Jewry until the Holocaust.

The answer to why there was so little assimilation of Jews in central and eastern Europe for so long would seem to lie in part in the probability that the alien surroundings in central and eastern Europe were not conducive, though contempt did not prevent some assimilation. Furthermore, Jews lived almost exclusively in shtetls, maintained a strong system of education for males, heeded rabbinic leadership, and scorned the life-style of their neighbors; and all of these tendencies increased with every outbreak of antisemitism.[69]

In the first half of the 11th century, Hai Gaon refers to questions that had been addressed to him from Ashkenaz, by which he undoubtedly means Germany. Rashi in the latter half of the 11th century refers to both the language of Ashkenaz[70] and the country of Ashkenaz.[71] During the 12th century, the word appears quite frequently. In the Mahzor Vitry, the kingdom of Ashkenaz is referred to chiefly in regard to the ritual of the synagogue there, but occasionally also with regard to certain other observances.[72]

In the literature of the 13th century, references to the land and the language of Ashkenaz often occur. Examples include Solomon ben Aderet's Responsa (vol. i., No. 395); the Responsa of Asher ben Jehiel (pp.4, 6); his Halakot (Berakot i. 12, ed. Wilna, p.10); the work of his son Jacob ben Asher, Tur Orach Chayim (chapter 59); the Responsa of Isaac ben Sheshet (numbers 193, 268, 270).

In the Midrash compilation, Genesis Rabbah, Rabbi Berechiah mentions Ashkenaz, Riphath, and Togarmah as German tribes or as German lands. It may correspond to a Greek word that may have existed in the Greek dialect of the Jews in Syria Palaestina, or the text is corrupted from "Germanica." This view of Berechiah is based on the Talmud (Yoma 10a; Jerusalem Talmud Megillah 71b), where Gomer, the father of Ashkenaz, is translated by Germamia, which evidently stands for Germany, and which was suggested by the similarity of the sound.

In later times, the word Ashkenaz is used to designate southern and western Germany, the ritual of which sections differs somewhat from that of eastern Germany and Poland. Thus the prayer-book of Isaiah Horowitz, and many others, give the piyyutim according to the Minhag of Ashkenaz and Poland.

According to 16th-century mystic Rabbi Elijah of Chelm, Ashkenazi Jews lived in Jerusalem during the 11th century. The story is told that a German-speaking Jew saved the life of a young German man surnamed Dolberger. So when the knights of the First Crusade came to siege Jerusalem, one of Dolberger's family members who was among them rescued Jews in Palestine and carried them back to Worms to repay the favor.[73] Further evidence of German communities in the holy city comes in the form of halakhic questions sent from Germany to Jerusalem during the second half of the 11th century.[74]

Material relating to the history of German Jews has been preserved in the communal accounts of certain communities on the Rhine, a Memorbuch, and a Liebesbrief, documents that are now part of the Sassoon Collection.[75]Heinrich Graetz has also added to the history of German Jewry in modern times in the abstract of his seminal work, History of the Jews, which he entitled "Volksthmliche Geschichte der Juden."

In an essay on Sephardi Jewry, Daniel Elazar at the Jerusalem Center for Public Affairs[76] summarized the demographic history of Ashkenazi Jews in the last thousand years, noting that at the end of the 11th century, 97% of world Jewry was Sephardic and 3% Ashkenazi; by the end of XVI century, the: 'Treaty on the redemption of captives', by Gracian of the God's Mother, Mercy Priest, who was imprisoned by Turks, cites a Tunisian Hebrew, made captive when arriving to Gaeta, who aided others with money, named: 'Simon Escanasi', in the mid-17th century, "Sephardim still outnumbered Ashkenazim three to two", but by the end of the 18th century, "Ashkenazim outnumbered Sephardim three to two, the result of improved living conditions in Christian Europe versus the Ottoman Muslim world."[76] By 1931, Ashkenazi Jews accounted for nearly 92% of world Jewry.[76] These factors are sheer demography showing the migration patterns of Jews from Southern and Western Europe to Central and Eastern Europe.

In 1740 a family from Lithuania became the first Ashkenazi Jews to settle in the Jewish Quarter of Jerusalem.[77]

In the generations after emigration from the west, Jewish communities in places like Poland, Russia, and Belarus enjoyed a comparatively stable socio-political environment. A thriving publishing industry and the printing of hundreds of biblical commentaries precipitated the development of the Hasidic movement as well as major Jewish academic centers.[78] After two centuries of comparative tolerance in the new nations, massive westward emigration occurred in the 19th and 20th centuries in response to pogroms in the east and the economic opportunities offered in other parts of the world. Ashkenazi Jews have made up the majority of the American Jewish community since 1750.[68]

In the context of the European Enlightenment, Jewish emancipation began in 18th century France and spread throughout Western and Central Europe. Disabilities that had limited the rights of Jews since the Middle Ages were abolished, including the requirements to wear distinctive clothing, pay special taxes, and live in ghettos isolated from non-Jewish communities, and the prohibitions on certain professions. Laws were passed to integrate Jews into their host countries, forcing Ashkenazi Jews to adopt family names (they had formerly used patronymics). Newfound inclusion into public life led to cultural growth in the Haskalah, or Jewish Enlightenment, with its goal of integrating modern European values into Jewish life.[79] As a reaction to increasing antisemitism and assimilation following the emancipation, Zionism was developed in central Europe.[80] Other Jews, particularly those in the Pale of Settlement, turned to socialism. These tendencies would be united in Labor Zionism, the founding ideology of the State of Israel.

Of the estimated 8.8 million Jews living in Europe at the beginning of World War II, the majority of whom were Ashkenazi, about 6 million more than two-thirds were systematically murdered in the Holocaust. These included 3 million of 3.3 million Polish Jews (91%); 900,000 of 1.5 million in Ukraine (60%); and 5090% of the Jews of other Slavic nations, Germany, Hungary, and the Baltic states, and over 25% of the Jews in France. Sephardi communities suffered similar depletions in a few countries, including Greece, the Netherlands and the former Yugoslavia.[81] As the large majority of the victims were Ashkenazi Jews, their percentage dropped from nearly 92% of world Jewry in 1931 to nearly 80% of world Jewry today.[76] The Holocaust also effectively put an end to the dynamic development of the Yiddish language in the previous decades, as the vast majority of the Jewish victims of the Holocaust, around 5 million, were Yiddish speakers.[82] Many of the surviving Ashkenazi Jews emigrated to countries such as Israel, Canada, Argentina, Australia, and the United States after the war.

Following the Holocaust, some sources place Ashkenazim today as making up approximately 8385 percent of Jews worldwide,[83][84][85][86] while Sergio DellaPergola in a rough calculation of Sephardic and Mizrahi Jews, implies that Ashkenazi make up a notably lower figure, less than 74%.[29] Other estimates place Ashkenazi Jews as making up about 75% of Jews worldwide.[30] Ashkenazi Jews constitute around 3536% of Israel's total population, or 47.5% of Israel's Jewish population.[87][88]

In Israel, the term Ashkenazi is now used in a manner unrelated to its original meaning, often applied to all Jews who settled in Europe and sometimes including those whose ethnic background is actually Sephardic. Jews of any non-Ashkenazi background, including Mizrahi, Yemenite, Kurdish and others who have no connection with the Iberian Peninsula, have similarly come to be lumped together as Sephardic. Jews of mixed background are increasingly common, partly because of intermarriage between Ashkenazi and non-Ashkenazi, and partly because many do not see such historic markers as relevant to their life experiences as Jews.[89]

Religious Ashkenazi Jews living in Israel are obliged to follow the authority of the chief Ashkenazi rabbi in halakhic matters. In this respect, a religiously Ashkenazi Jew is an Israeli who is more likely to support certain religious interests in Israel, including certain political parties. These political parties result from the fact that a portion of the Israeli electorate votes for Jewish religious parties; although the electoral map changes from one election to another, there are generally several small parties associated with the interests of religious Ashkenazi Jews. The role of religious parties, including small religious parties that play important roles as coalition members, results in turn from Israel's composition as a complex society in which competing social, economic, and religious interests stand for election to the Knesset, a unicameral legislature with 120 seats.[90]

People of Ashkenazi descent constitute around 47.5% of Israeli Jews (and therefore 3536% of Israelis).[4] They have played a prominent role in the economy, media, and politics[91] of Israel since its founding. During the first decades of Israel as a state, strong cultural conflict occurred between Sephardic and Ashkenazi Jews (mainly east European Ashkenazim). The roots of this conflict, which still exists to a much smaller extent in present-day Israeli society, are chiefly attributed to the concept of the "melting pot".[92] That is to say, all Jewish immigrants who arrived in Israel were strongly encouraged to "melt down" their own particular exilic identities within the general social "pot" in order to become Israeli.[93]

The Ashkenazi Chief Rabbis in the Yishuv and Israel include:

Religious Jews have Minhagim, customs, in addition to Halakha, or religious law, and different interpretations of law. Different groups of religious Jews in different geographic areas historically adopted different customs and interpretations. On certain issues, Orthodox Jews are required to follow the customs of their ancestors, and do not believe they have the option of picking and choosing. For this reason, observant Jews at times find it important for religious reasons to ascertain who their household's religious ancestors are in order to know what customs their household should follow. These times include, for example, when two Jews of different ethnic background marry, when a non-Jew converts to Judaism and determines what customs to follow for the first time, or when a lapsed or less observant Jew returns to traditional Judaism and must determine what was done in his or her family's past. In this sense, "Ashkenazic" refers both to a family ancestry and to a body of customs binding on Jews of that ancestry. Reform Judaism, which does not necessarily follow those minhagim, did nonetheless originate among Ashkenazi Jews.[94]

In a religious sense, an Ashkenazi Jew is any Jew whose family tradition and ritual follows Ashkenazi practice. Until the Ashkenazi community first began to develop in the Early Middle Ages, the centers of Jewish religious authority were in the Islamic world, at Baghdad and in Islamic Spain. Ashkenaz (Germany) was so distant geographically that it developed a minhag of its own. Ashkenazi Hebrew came to be pronounced in ways distinct from other forms of Hebrew.[95]

In this respect, the counterpart of Ashkenazi is Sephardic, since most non-Ashkenazi Orthodox Jews follow Sephardic rabbinical authorities, whether or not they are ethnically Sephardic. By tradition, a Sephardic or Mizrahi woman who marries into an Orthodox or Haredi Ashkenazi Jewish family raises her children to be Ashkenazi Jews; conversely an Ashkenazi woman who marries a Sephardi or Mizrahi man is expected to take on Sephardic practice and the children inherit a Sephardic identity, though in practice many families compromise. A convert generally follows the practice of the beth din that converted him or her. With the integration of Jews from around the world in Israel, North America, and other places, the religious definition of an Ashkenazi Jew is blurring, especially outside Orthodox Judaism.[96]

New developments in Judaism often transcend differences in religious practice between Ashkenazi and Sephardic Jews. In North American cities, social trends such as the chavurah movement, and the emergence of "post-denominational Judaism"[97][98] often bring together younger Jews of diverse ethnic backgrounds. In recent years, there has been increased interest in Kabbalah, which many Ashkenazi Jews study outside of the Yeshiva framework. Another trend is the new popularity of ecstatic worship in the Jewish Renewal movement and the Carlebach style minyan, both of which are nominally of Ashkenazi origin.[99]

Culturally, an Ashkenazi Jew can be identified by the concept of Yiddishkeit, which means "Jewishness" in the Yiddish language.[100]Yiddishkeit is specifically the Jewishness of Ashkenazi Jews.[101] Before the Haskalah and the emancipation of Jews in Europe, this meant the study of Torah and Talmud for men, and a family and communal life governed by the observance of Jewish Law for men and women. From the Rhineland to Riga to Romania, most Jews prayed in liturgical Ashkenazi Hebrew, and spoke Yiddish in their secular lives. But with modernization, Yiddishkeit now encompasses not just Orthodoxy and Hasidism, but a broad range of movements, ideologies, practices, and traditions in which Ashkenazi Jews have participated and somehow retained a sense of Jewishness. Although a far smaller number of Jews still speak Yiddish, Yiddishkeit can be identified in manners of speech, in styles of humor, in patterns of association. Broadly speaking, a Jew is one who associates culturally with Jews, supports Jewish institutions, reads Jewish books and periodicals, attends Jewish movies and theater, travels to Israel, visits historical synagogues, and so forth. It is a definition that applies to Jewish culture in general, and to Ashkenazi Yiddishkeit in particular.

As Ashkenazi Jews moved away from Europe, mostly in the form of aliyah to Israel, or immigration to North America, and other English-speaking areas such as South Africa; and Europe (particularly France) and Latin America, the geographic isolation that gave rise to Ashkenazim has given way to mixing with other cultures, and with non-Ashkenazi Jews who, similarly, are no longer isolated in distinct geographic locales. Hebrew has replaced Yiddish as the primary Jewish language for many Ashkenazi Jews, although many Hasidic and Hareidi groups continue to use Yiddish in daily life. (There are numerous Ashkenazi Jewish anglophones and Russian-speakers as well, although English and Russian are not originally Jewish languages.)

France's blended Jewish community is typical of the cultural recombination that is going on among Jews throughout the world. Although France expelled its original Jewish population in the Middle Ages, by the time of the French Revolution, there were two distinct Jewish populations. One consisted of Sephardic Jews, originally refugees from the Inquisition and concentrated in the southwest, while the other community was Ashkenazi, concentrated in formerly German Alsace, and mainly speaking a German dialect similar to Yiddish. (A third community of Provenal Jews living in Comtat Venaissin were technically outside France, and were later absorbed into the Sephardim.) The two communities were so separate and different that the National Assembly emancipated them separately in 1790 and 1791.[102]

But after emancipation, a sense of a unified French Jewry emerged, especially when France was wracked by the Dreyfus affair in the 1890s. In the 1920s and 1930s, Ashkenazi Jews from Europe arrived in large numbers as refugees from antisemitism, the Russian revolution, and the economic turmoil of the Great Depression. By the 1930s, Paris had a vibrant Yiddish culture, and many Jews were involved in diverse political movements. After the Vichy years and the Holocaust, the French Jewish population was augmented once again, first by Ashkenazi refugees from Central Europe, and later by Sephardi immigrants and refugees from North Africa, many of them francophone.

Then, in the 1990s, yet another Ashkenazi Jewish wave began to arrive from countries of the former Soviet Union and Central Europe. The result is a pluralistic Jewish community that still has some distinct elements of both Ashkenazi and Sephardic culture. But in France, it is becoming much more difficult to sort out the two, and a distinctly French Jewishness has emerged.[103]

In an ethnic sense, an Ashkenazi Jew is one whose ancestry can be traced to the Jews who settled in Central Europe. For roughly a thousand years, the Ashkenazim were a reproductively isolated population in Europe, despite living in many countries, with little inflow or outflow from migration, conversion, or intermarriage with other groups, including other Jews. Human geneticists have argued that genetic variations have been identified that show high frequencies among Ashkenazi Jews, but not in the general European population, be they for patrilineal markers (Y-chromosome haplotypes) and for matrilineal markers (mitotypes).[104] Since the middle of the 20th century, many Ashkenazi Jews have intermarried, both with members of other Jewish communities and with people of other nations and faiths.[105]

A 2006 study found Ashkenazi Jews to be a clear, homogeneous genetic subgroup. Strikingly, regardless of the place of origin, Ashkenazi Jews can be grouped in the same genetic cohort that is, regardless of whether an Ashkenazi Jew's ancestors came from Poland, Russia, Hungary, Lithuania, or any other place with a historical Jewish population, they belong to the same ethnic group. The research demonstrates the endogamy of the Jewish population in Europe and lends further credence to the idea of Ashkenazi Jews as an ethnic group. Moreover, though intermarriage among Jews of Ashkenazi descent has become increasingly common, many Haredi Jews, particularly members of Hasidic or Hareidi sects, continue to marry exclusively fellow Ashkenazi Jews. This trend keeps Ashkenazi genes prevalent and also helps researchers further study the genes of Ashkenazi Jews with relative ease. It is noteworthy that these Haredi Jews often have extremely large families.[10]

The Halakhic practices of (Orthodox) Ashkenazi Jews may differ from those of Sephardi Jews, particularly in matters of custom. Differences are noted in the Shulkhan Arukh itself, in the gloss of Moses Isserles. Well known differences in practice include:

The term Ashkenazi also refers to the nusach Ashkenaz (Hebrew, "liturgical tradition", or rite) used by Ashkenazi Jews in their Siddur (prayer book). A nusach is defined by a liturgical tradition's choice of prayers, order of prayers, text of prayers and melodies used in the singing of prayers. Two other major forms of nusach among Ashkenazic Jews are Nusach Sefard (not to be confused with the Sephardic ritual), which is the general Polish Hasidic nusach, and Nusach Ari, as used by Lubavitch Hasidim.

Several famous people have Ashkenazi as a surname, such as Vladimir Ashkenazy. However, most people with this surname hail from within Sephardic communities, particularly from the Syrian Jewish community. The Sephardic carriers of the surname would have some Ashkenazi ancestors since the surname was adopted by families who were initially of Ashkenazic origins who moved to Sephardi countries and joined those communities. Ashkenazi would be formally adopted as the family surname having started off as a nickname imposed by their adopted communities. Some have shortened the name to Ash.

Relations between Ashkenazim and Sephardim have not always been warm. North African Sepharadim and Berber Jews were often looked upon by Ashkenazim as second-class citizens during the first decade after the creation of Israel. This has led to protest movements such as the Israeli Black Panthers led by Saadia Marciano a Moroccan Jew. Nowadays, relations are getting better.[107] In some instances, Ashkenazi communities have accepted significant numbers of Sephardi newcomers, sometimes resulting in intermarriage.[108][109]

Ashkenazi Jews have a noted history of achievement in Western societies[110] in the fields of exact and social sciences, literature, finance, politics, media, and others. In those societies where they have been free to enter any profession, they have a record of high occupational achievement, entering professions and fields of commerce where higher education is required.[111] Ashkenazi Jews have won a large number of the Nobel awards.[112][113] While they make up about 2% of the U.S. population,[114] 27% of United States Nobel prize winners in the 20th century,[114] a quarter of Fields Medal winners,[115] 25% of ACM Turing Award winners,[114] half the world's chess champions,[114] including 8% of the top 100 world chess players,[116] and a quarter of Westinghouse Science Talent Search winners[115] have Ashkenazi Jewish ancestry.

Time magazine's person of the 20th century, Albert Einstein,[117] was an Ashkenazi Jew. According to a study performed by Cambridge University, 21% of Ivy League students, 25% of the Turing Award winners, 23% of the wealthiest Americans, and 38% of the Oscar-winning film directors, and 29% of Oslo awardees are Ashkenazi Jews.[118]

Efforts to identify the origins of Ashkenazi Jews through DNA analysis began in the 1990s. Currently, there are three types of genetic origin testing, autosomal DNA (atDNA), mitochondrial DNA (mtDNA), and Y-chromosomal DNA (Y-DNA). Autosomal DNA is a mixture from an individual's entire ancestry, Y-DNA shows a male's lineage only along his strict-paternal line, mtDNA shows any person's lineage only along the strict-maternal line. Genome-wide association studies have also been employed to yield findings relevant to genetic origins.

Like most DNA studies of human migration patterns, the earliest studies on Ashkenazi Jews focused on the Y-DNA and mtDNA segments of the human genome. Both segments are unaffected by recombination (except for the ends of the Y chromosome the pseudoautosomal regions known as PAR1 and PAR2), thus allowing tracing of direct maternal and paternal lineages.

These studies revealed that Ashkenazi Jews originate from an ancient (2000 BCE - 700 BCE) population of the Middle East who had spread to Europe.[119] Ashkenazic Jews display the homogeneity of a genetic bottleneck, meaning they descend from a larger population whose numbers were greatly reduced but recovered through a few founding individuals. Although the Jewish people in general were present across a wide geographical area as described, genetic research done by Gil Atzmon of the Longevity Genes Project at Albert Einstein College of Medicine suggests "that Ashkenazim branched off from other Jews around the time of the destruction of the First Temple, 2,500 years ago ... flourished during the Roman Empire but then went through a 'severe bottleneck' as they dispersed, reducing a population of several million to just 400 families who left Northern Italy around the year 1000 for Central and eventually Eastern Europe."[120]

Various studies have arrived at diverging conclusions regarding both the degree and the sources of the non-Levantine admixture in Ashkenazim,[31] particularly with respect to the extent of the non-Levantine genetic origin observed in Ashkenazi maternal lineages, which is in contrast to the predominant Levantine genetic origin observed in Ashkenazi paternal lineages. All studies nevertheless agree that genetic overlap with the Fertile Crescent exists in both lineages, albeit at differing rates. Collectively, Ashkenazi Jews are less genetically diverse than other Jewish ethnic divisions, due to their genetic bottleneck.[121]

The majority of genetic findings to date concerning Ashkenazi Jews conclude that the male line was founded by ancestors from the Middle East.[122][123][124] Others have found a similar genetic line among Greeks, and Macedonians.[citation needed]

A study of haplotypes of the Y-chromosome, published in 2000, addressed the paternal origins of Ashkenazi Jews. Hammer et al.[125] found that the Y-chromosome of Ashkenazi and Sephardic Jews contained mutations that are also common among other Middle Eastern peoples, but uncommon in the autochthonous European population. This suggested that the male ancestors of the Ashkenazi Jews could be traced mostly to the Middle East. The proportion of male genetic admixture in Ashkenazi Jews amounts to less than 0.5% per generation over an estimated 80 generations, with "relatively minor contribution of European Y chromosomes to the Ashkenazim," and a total admixture estimate "very similar to Motulsky's average estimate of 12.5%." This supported the finding that "Diaspora Jews from Europe, Northwest Africa, and the Near East resemble each other more closely than they resemble their non-Jewish neighbors." "Past research found that 5080 percent of DNA from the Ashkenazi Y chromosome, which is used to trace the male lineage, originated in the Near East," Richards said.

The population has subsequently spread out. Based on accounts such as those of Jewish historian Flavius Josephus, by the time of the destruction of the Second Temple in 70 CE, as many as six million Jews were already living in the Roman Empire, but outside Israel, mainly in Italy and Southern Europe. In contrast, only about 500,000 lived in Judea, said Ostrer, who was not involved in the new study.[126]

A 2001 study by Nebel et al. showed that both Ashkenazi and Sephardic Jewish populations share the same overall paternal Near Eastern ancestries. In comparison with data available from other relevant populations in the region, Jews were found to be more closely related to groups in the north of the Fertile Crescent. The authors also report on Eu 19 (R1a) chromosomes, which are very frequent in Central and Eastern Europeans (54%60%) at elevated frequency (12.7%) in Ashkenazi Jews. They hypothesized that the differences among Ashkenazim Jews could reflect low-level gene flow from surrounding European populations or genetic drift during isolation.[127] A later 2005 study by Nebel et al., found a similar level of 11.5% of male Ashkenazim belonging to R1a1a (M17+), the dominant Y-chromosome haplogroup in Central and Eastern Europeans.[128]

Before 2006, geneticists had largely attributed the ethnogenesis of most of the world's Jewish populations, including Ashkenazi Jews, to Israelite Jewish male migrants from the Middle East and "the women from each local population whom they took as wives and converted to Judaism." Thus, in 2002, in line with this model of origin, David Goldstein, now of Duke University, reported that unlike male Ashkenazi lineages, the female lineages in Ashkenazi Jewish communities "did not seem to be Middle Eastern", and that each community had its own genetic pattern and even that "in some cases the mitochondrial DNA was closely related to that of the host community." In his view this suggested "that Jewish men had arrived from the Middle East, taken wives from the host population and converted them to Judaism, after which there was no further intermarriage with non-Jews."[104]

In 2006, a study by Behar et al.,[129] based on what was at that time high-resolution analysis of haplogroup K (mtDNA), suggested that about 40% of the current Ashkenazi population is descended matrilineally from just four women, or "founder lineages", that were "likely from a Hebrew/Levantine mtDNA pool" originating in the Middle East in the 1st and 2nd centuries CE. Additionally, Behar et al. suggested that the rest of Ashkenazi mtDNA is originated from ~150 women, and that most of those were also likely of Middle Eastern origin.[129] In reference specifically to Haplogroup K, they suggested that although it is common throughout western Eurasia, "the observed global pattern of distribution renders very unlikely the possibility that the four aforementioned founder lineages entered the Ashkenazi mtDNA pool via gene flow from a European host population".

In 2013, however, a study of Ashkenazi mitochondrial DNA by a team led by Martin B. Richards of the University of Huddersfield in England reached different conclusions, corroborating the pre-2006 origin hypothesis. Testing was performed on the full 16,600 DNA units composing mitochondrial DNA (the 2006 Behar study had only tested 1,000 units) in all their subjects, and the study found that the four main female Ashkenazi founders had descent lines that were established in Europe 10,000 to 20,000 years in the past[130] while most of the remaining minor founders also have a deep European ancestry. The study states that the great majority of Ashkenazi maternal lineages were not brought from the Near East (i.e., they were non-Israelite), nor were they recruited in the Caucasus (i.e., they were non-Khazar), but instead they were assimilated within Europe, primarily of Italian and Old French origins. Richards summarized the findings on the female line as such: "[N]one [of the mtDNA] came from the North Caucasus, located along the border between Europe and Asia between the Black and Caspian seas. All of our presently available studies including my own, should thoroughly debunk one of the most questionable, but still tenacious, hypotheses: that most Ashkenazi Jews can trace their roots to the mysterious Khazar Kingdom that flourished during the ninth century in the region between the Byzantine Empire and the Persian Empire."[126] The 2013 study estimated that 80 percent of Ashkenazi maternal ancestry comes from women indigenous to Europe, and only 8 percent from the Near East, while the origin of the remainder is undetermined.[12][130] According to the study these findings "point to a significant role for the conversion of women in the formation of Ashkenazi communities."[12][13][131][132][133][134]Karl Skorecki at Technion criticized the study for perceived flaws in phylogenetic analysis. "While Costa et al have re-opened the question of the maternal origins of Ashkenazi Jewry, the phylogenetic analysis in the manuscript does not 'settle' the question."[135]

A 2014 study by Fernndez et al. has found that Ashkenazi Jews display a frequency of haplogroup K in their maternal DNA that suggests an ancient Near Eastern origin, similar to the results of Behar. He stated that this observation clearly contradicts the results of the study led by Richards that suggested a European source for 3 exclusively Ashkenazi K lineages.[136]

In genetic epidemiology, a genome-wide association study (GWA study, or GWAS) is an examination of all or most of the genes (the genome) of different individuals of a particular species to see how much the genes vary from individual to individual. These techniques were originally designed for epidemiological uses, to identify genetic associations with observable traits.[137]

A 2006 study by Seldin et al. used over five thousand autosomal SNPs to demonstrate European genetic substructure. The results showed "a consistent and reproducible distinction between 'northern' and 'southern' European population groups". Most northern, central, and eastern Europeans (Finns, Swedes, English, Irish, Germans, and Ukrainians) showed >90% in the "northern" population group, while most individual participants with southern European ancestry (Italians, Greeks, Portuguese, Spaniards) showed >85% in the "southern" group. Both Ashkenazi Jews as well as Sephardic Jews showed >85% membership in the "southern" group. Referring to the Jews clustering with southern Europeans, the authors state the results were "consistent with a later Mediterranean origin of these ethnic groups".[10]

A 2007 study by Bauchet et al. found that Ashkenazi Jews were most closely clustered with Arabic North African populations when compared to Global population, and in the European structure analysis, they share similarities only with Greeks and Southern Italians, reflecting their east Mediterranean origins.[138][139]

A 2010 study on Jewish ancestry by Atzmon-Ostrer et al. stated "Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry", as both groups the Middle Eastern Jews and European/Syrian Jews shared common ancestors in the Middle East about 2500 years ago. The study examines genetic markers spread across the entire genome and shows that the Jewish groups (Ashkenazi and non Ashkenazi) share large swaths of DNA, indicating close relationships and that each of the Jewish groups in the study (Iranian, Iraqi, Syrian, Italian, Turkish, Greek and Ashkenazi) has its own genetic signature but is more closely related to the other Jewish groups than to their fellow non-Jewish countrymen.[140] Atzmon's team found that the SNP markers in genetic segments of 3 million DNA letters or longer were 10 times more likely to be identical among Jews than non-Jews. Results of the analysis also tally with biblical accounts of the fate of the Jews. The study also found that with respect to non-Jewish European groups, the population most closely related to Ashkenazi Jews are modern-day Italians. The study speculated that the genetic-similarity between Ashkenazi Jews and Italians may be due to inter-marriage and conversions in the time of the Roman Empire. It was also found that any two Ashkenazi Jewish participants in the study shared about as much DNA as fourth or fifth cousins.[141][142]

A 2010 study by Bray et al., using SNP microarray techniques and linkage analysis found that when assuming Druze and Palestinian Arab populations to represent the reference to world Jewry ancestor genome, between 35 and 55 percent of the modern Ashkenazi genome can possibly be of European origin, and that European "admixture is considerably higher than previous estimates by studies that used the Y chromosome" with this reference point. Assuming this reference point the linkage disequilibrium in the Ashkenazi Jewish population was interpreted as "matches signs of interbreeding or 'admixture' between Middle Eastern and European populations".[143] On the Bray et al. tree, Ashkenazi Jews were found to be a genetically more divergent population than Russians, Orcadians, French, Basques, Italians, Sardinians and Tuscans. The study also observed that Ashkenazim are more diverse than their Middle Eastern relatives, which was counterintuitive because Ashkenazim are supposed to be a subset, not a superset, of their assumed geographical source population. Bray et al. therefore postulate that these results reflect not the population antiquity but a history of mixing between genetically distinct populations in Europe. However, it's possible that the relaxation of marriage prescription in the ancestors of Ashkenazim that drove their heterozygosity up, while the maintenance of the FBD rule in native Middle Easterners have been keeping their heterozygosity values in check. Ashkenazim distinctiveness as found in the Bray et al. study, therefore, may come from their ethnic endogamy (ethnic inbreeding), which allowed them to "mine" their ancestral gene pool in the context of relative reproductive isolation from European neighbors, and not from clan endogamy (clan inbreeding). Consequently, their higher diversity compared to Middle Easterners stems from the latter's marriage practices, not necessarily from the former's admixture with Europeans.[144]

The genome-wide genetic study carried out in 2010 by Behar et al. examined the genetic relationships among all major Jewish groups, including Ashkenazim, as well as the genetic relationship between these Jewish groups and non-Jewish ethnic populations. The study found that contemporary Jews (excluding Indian and Ethiopian Jews) have a close genetic relationship with people from the Levant. The authors explained that "the most parsimonious explanation for these observations is a common genetic origin, which is consistent with an historical formulation of the Jewish people as descending from ancient Hebrew and Israelite residents of the Levant".[145]

A 2015 study by James Xue et al. results suggested that 75% of the European ancestry in AJ is South-European, with the rest mostly East European. The time of admixture was inferred to be around 30-40 generations ago, on the eve of the Ashkenazi settlement in Eastern-Europe.[146]

In the late 19th century, it was proposed that the core of today's Ashkenazi Jewry are genetically descended from a hypothetical Khazarian Jewish diaspora who had migrated westward from modern Russia and Ukraine into modern France and Germany (as opposed to the currently held theory that Jews from France and Germany migrated into Eastern Europe). The hypothesis is not corroborated by historical sources[147] and is unsubstantiated by genetics, but it is still occasionally supported by scholars who have had some success in keeping the theory in the academic conscience.[148] The theory is associated with antisemitism[149] and anti-Zionism.[150][151]

A 2013 trans-genome study carried out by 30 geneticists, from 13 universities and academies, from 9 countries, assembling the largest data set available to date, for assessment of Ashkenazi Jewish genetic origins found no evidence of Khazar origin among Ashkenazi Jews. "Thus, analysis of Ashkenazi Jews together with a large sample from the region of the Khazar Khaganate corroborates the earlier results that Ashkenazi Jews derive their ancestry primarily from populations of the Middle East and Europe, that they possess considerable shared ancestry with other Jewish populations, and that there is no indication of a significant genetic contribution either from within or from north of the Caucasus region", the authors concluded.[152]

There are many references to Ashkenazi Jews in the literature of medical and population genetics. Indeed, much awareness of "Ashkenazi Jews" as an ethnic group or category stems from the large number of genetic studies of disease, including many that are well reported in the media, that have been conducted among Jews. Jewish populations have been studied more thoroughly than most other human populations, for a variety of reasons:

The result is a form of ascertainment bias. This has sometimes created an impression that Jews are more susceptible to genetic disease than other populations.[153] Healthcare professionals are often taught to consider those of Ashkenazi descent to be at increased risk for colon cancer.[154]

Genetic counseling and genetic testing are often undertaken by couples where both partners are of Ashkenazi ancestry. Some organizations, most notably Dor Yeshorim, organize screening programs to prevent homozygosity for the genes that cause related diseases.[155][156]

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Medical genetics of Jews – Wikipedia

Thursday, December 1st, 2016

The medical genetics of Jews is the study, screening, and treatment of genetic disorders more common in particular Jewish populations than in the population as a whole.[1] The genetics of Ashkenazi Jews have been particularly well-studied, resulting in the discovery of many genetic disorders associated with this ethnic group. In contrast, the medical genetics of Sephardic Jews and Mizrahi Jews are more complicated, since they are more genetically diverse and consequently no genetic disorders are more common in these groups as a whole; instead, they tend to have the genetic diseases common in their various countries of origin.[1][2] Several organizations, such as Dor Yeshorim,[3] offer screening for Ashkenazi genetic diseases, and these screening programs have had a significant impact, in particular by reducing the number of cases of TaySachs disease.[4]

Different ethnic groups tend to suffer from different rates of hereditary diseases, with some being more common, and some less common. Hereditary diseases, particularly hemophilia, were recognized early in Jewish history, even being described in the Talmud.[5] However, the scientific study of hereditary disease in Jewish populations was initially hindered by scientific racism, which is based on racial supremacism.[6][7]

However, modern studies on the genetics of particular ethnic groups have the tightly defined purpose of avoiding the birth of children with genetic diseases, or identifying people at particular risk of developing a disease in the future.[6] Consequently, the Jewish community has been very supportive of modern genetic testing programs, although this unusually high degree of cooperation has raised concerns that it might lead to the false perception that Jews are more susceptible to genetic diseases than other groups of people.[5]

However, most populations contain hundreds of alleles that could potentially cause disease and most people are heterozygotes for one or two recessive alleles that would be lethal in a homozygote.[8] Although the overall frequency of disease-causing alleles does not vary much between populations, the practice of consanguineous marriage (marriage between second cousins or closer relatives) is common in some Jewish communities, which produces a small increase in the number of children with congenital defects.[9]

According to Daphna Birenbaum Carmeli at the University of Haifa, Jewish populations have been studied more thoroughly than most other human populations because:[10]

The result is a form of ascertainment bias. This has sometimes created an impression that Jews are more susceptible to genetic disease than other populations. Carmeli writes, "Jews are over-represented in human genetic literature, particularly in mutation-related contexts."[10] Another factor that may aid genetic research in this community is that Jewish culture results in excellent medical care, which is coupled to a strong interest in the community's history and demography.[11]

This set of advantages have led to Ashkenazi Jews in particular being used in many genetic studies, not just in the study of genetic diseases. For example, a series of publications on Ashkenazi centenarians established their longevity was strongly inherited and associated with lower rates of age-related diseases.[12] This "healthy aging" phenotype may be due to higher levels of telomerase in these individuals.[13]

The most detailed genetic analysis study of Ashkenazi was published in September 2014 by Shai Carmon and his team at Columbia University. The results of the detailed study show that today's 10 million Ashkenazi Jews descend from a population of only 350 individuals who lived about 600800 years ago. That population derived from both Europe and the Middle East.[14] There is evidence that the population bottleneck may have allowed deleterious alleles to become more prevalent in the population due to genetic drift.[15] As a result, this group has been particularly intensively studied, so many mutations have been identified as common in Ashkenazis.[16] Of these diseases, many also occur in other Jewish groups and in non-Jewish populations, although the specific mutation which causes the disease may vary between populations. For example, two different mutations in the glucocerebrosidase gene causes Gaucher's disease in Ashkenazis, which is their most common genetic disease, but only one of these mutations is found in non-Jewish groups.[4] A few diseases are unique to this group; for example, familial dysautonomia is almost unknown in other populations.[4]

TaySachs disease, which can present as a fatal illness of children that causes mental deterioration prior to death, was historically more prevalent among Ashkenazi Jews,[18] although high levels of the disease are also found in some Pennsylvania Dutch, southern Louisiana Cajun, and eastern Quebec French Canadian populations.[19] Since the 1970s, however, proactive genetic testing has been quite effective in eliminating TaySachs from the Ashkenazi Jewish population.[20]

Gaucher's disease, in which lipids accumulate in inappropriate locations, occurs most frequently among Ashkenazi Jews;[21] the mutation is carried by roughly one in every 15 Ashkenazi Jews, compared to one in 100 of the general American population.[22] Gaucher's disease can cause brain damage and seizures, but these effects are not usually present in the form manifested among Ashkenazi Jews; while sufferers still bruise easily, and it can still potentially rupture the spleen, it generally has only a minor impact on life expectancy.

Ashkenazi Jews are also highly affected by other lysosomal storage diseases, particularly in the form of lipid storage disorders. Compared to other ethnic groups, they more frequently act as carriers of mucolipidosis[23] and NiemannPick disease,[24] the latter of which can prove fatal.

The occurrence of several lysosomal storage disorders in the same population suggests the alleles responsible might have conferred some selective advantage in the past.[25] This would be similar to the hemoglobin allele which is responsible for sickle-cell disease, but solely in people with two copies; those with just one copy of the allele have a sickle cell trait and gain partial immunity to malaria as a result. This effect is called heterozygote advantage.[26]

Some of these disorders may have become common in this population due to selection for high levels of intelligence (see Ashkenazi intelligence).[27][28] However, other research suggests no difference is found between the frequency of this group of diseases and other genetic diseases in Ashkenazis, which is evidence against any specific selectivity towards lysosomal disorders.[29]

Familial dysautonomia (RileyDay syndrome), which causes vomiting, speech problems, an inability to cry, and false sensory perception, is almost exclusive to Ashkenazi Jews;[30] Ashkenazi Jews are almost 100 times more likely to carry the disease than anyone else.[31]

Diseases inherited in an autosomal recessive pattern often occur in endogamous populations. Among Ashkenazi Jews, a higher incidence of specific genetic disorders and hereditary diseases have been verified, including:

In contrast to the Ashkenazi population, Sephardic and Mizrahi Jews are much more divergent groups, with ancestors from Spain, Portugal, Morocco, Tunisia, Algeria, Italy, Libya, the Balkans, Iran, Iraq, India, and Yemen, with specific genetic disorders found in each regional group, or even in specific subpopulations in these regions.[1]

One of the first genetic testing programs to identify heterozygote carriers of a genetic disorder was a program aimed at eliminating TaySachs disease. This program began in 1970, and over one million people have now been screened for the mutation.[50] Identifying carriers and counseling couples on reproductive options have had a large impact on the incidence of the disease, with a decrease from 4050 per year worldwide to only four or five per year.[4] Screening programs now test for several genetic disorders in Jews, although these focus on the Ashkenazi Jews, since other Jewish groups cannot be given a single set of tests for a common set of disorders.[2] In the USA, these screening programs have been widely accepted by the Ashkenazi community, and have greatly reduced the frequency of the disorders.[51]

Prenatal testing for several genetic diseases is offered as commercial panels for Ashkenazi couples by both CIGNA and Quest Diagnostics. The CIGNA panel is available for testing for parental/preconception screening or following chorionic villus sampling or amniocentesis and tests for Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia, Gaucher disease, mucolipidosis IV, Neimann-Pick disease type A, Tay-Sachs disease, and torsion dystonia. The Quest panel is for parental/preconception testing and tests for Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Neimann-Pick disease types A and B and Tay-Sachs disease.

The official recommendations of the American College of Obstetricians and Gynecologists is that Ashkenazi individuals be offered screening for Tay Sachs, Canavan, cystic fibrosis, and familial dysautonomia as part of routine obstetrical care.[52]

In the orthodox community, an organization called Dor Yeshorim carries out anonymous genetic screening of couples before marriage to reduce the risk of children with genetic diseases being born.[53] The program educates young people on medical genetics and screens school-aged children for any disease genes. These results are then entered into an anonymous database, identified only by a unique ID number given to the person who was tested. If two people are considering getting married, they call the organization and tell them their ID numbers. The organization then tells them if they are genetically compatible. It is not divulged if one member is a carrier, so as to protect the carrier and his or her family from stigmatization.[53] However, this program has been criticized for exerting social pressure on people to be tested, and for screening for a broad range of recessive genes, including disorders such as Gaucher's disease.[3]

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normande genetics: sustainable genetics that breed quality

Wednesday, November 23rd, 2016

Experience Normande genetics

Another breeding season is here, along with a new opportunity to experience Normande genetics. Please take a look at our Fall 2016proofsand, if it's your first time, take a leap of faith! Whether you graze or not, crossing with Normande offers many benefits. Check our the various pages of our website for more details about the breed's many strong qualities. See more information on ourcatalog pageon how to choose our bulls. As usual, graziers are advised to focus on bulls with low stature indexes for medium size cows if they cross with Holsteins. Low stature is less important if you cross with Jerseys. Finally, do not forget to follow us on Facebook and Twitter for quicker and more frequent news updates.

Normande Genetics was created in 1997 to bring the top dairy genetics of the Normande breed to the American dairyland. Because the U.S. dairy industry had long since cut its grass roots in favor of intensive, high-energy, grain-based systems, we believed that genetics here were no longer well suited to grass-based operations. That insight has been confirmed consistently in interactions with American dairy farmers, whose herds are suffering loss of functionality in fertility and longevity, owing to over-selection for productivity, and secondarily, dairyness.

Originally focused on grazing daires, we quickly realize that the need for different genetics applies to all dairies, and includes conventional ones. Intensive operations are increasingly faced with fertility and health issues, and many of these issues can be attributed to frail genetics or inbreeding.

While the U.S. dairy sire selection process has started to move towards improving functional traits, it will take time to see results in the field. In addition, in-breeding and a narrowing gene pool for most dairy breeds worldwide add to the problem, so there is no easy and short-term answer to the weakening of health traits.

Thats why crossbreeding makes sense. After all, dairy farmers want to lower their cost of operation while increasing their revenue, which means profits and margins replace production as the main benchmarks of success. In turn, genetic traits that contribute to the bottom line become essential, while selecting for milk production becomes relatively less important. For more information about why crossbreeding is a useful tool, you can download this article:

download "Why Crossbreeding?" Article (PDF)

The Normandes traits serve the objectives of both grass-based and conventional operations in two ways: bringing strength and functionality while adding value whenever possible. The Normande has outstanding attributes as a purebred or in a cross-breeding program. The breed has shown successful examples with all U.S. dairy breeds and is often included in three-way crossbreeding programs. The University of Minnesotas new experimental organic herd includes such a cross.

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Population Reference Bureau (PRB)

Thursday, November 17th, 2016

Regions / Countries

Select Country Afghanistan Albania Algeria American Samoa Andorra Angola Anguilla Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia-Herzegovina Botswana Brazil Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Central African Republic Chad Channel Islands Chile China Hong Kong, SAR Macao, SAR Colombia Comoros Congo Congo, Dem. Rep. of Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Timor-Leste Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Fiji Finland France French Guiana French Polynesia Gabon Gambia Georgia Germany Ghana Greece Greenland Grenada Guadeloupe Guam Guatemala Guinea Guinea-Bissau Guyana Haiti Honduras Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jordan Kazakhstan Kenya Kiribati Korea, North Korea, South Kuwait Kyrgyzstan Laos Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macedonia Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mexico Federated States of Micronesia Moldova Monaco Mongolia Montenegro Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Poland Portugal Puerto Rico Qatar Reunion Romania Russia Rwanda Samoa Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa Spain Sri Lanka St. Kitts-Nevis St. Lucia St. Vincent & the Grenadines Sudan Suriname Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand Togo Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela Vietnam Western Sahara Yemen Zambia Zimbabwe

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Supercourse: Epidemiology, the Internet, and Global Health

Thursday, September 8th, 2016

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Academic research council

Achievements public health

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Acne therapeutic strategies

Acute coronary symptoms

Acute coronary syndromes

Adenoviridae and iridoviridae

Adherence hypertension treatment

Administration management medical organizations

Adolescent health risk behavior

Adolescents reproductive health

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Adverse drug reactions

Advocacy strategy planning

African sleeping sickness

Aids/ hiv current senario

Airborne contaminants

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Aminoglycosidearginine conjugates

Analytic epidemiology

Anaplasmosis taxonomic

Anemia family practice

Anger regulation interventions

Antimicrobial resistance

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Antiretroviral agents

Assessing disease frequency

Assessment bioterrorism threat

Assessment nutritional

Assistive technology devices

Attack preparedness events

Avian influenza: zoonosis

Bacterial membrane vesicles

Bacterial vaginosis pregnancy

Bases of biostatistics

Behaviour medical sciences

Betaserk treatment stroke

Bias confounding chance

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Binomial distribution

Biochemical system medicine

Biological challenges

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Biostatistics

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Bmj triages manuscripts

Body fluid volume regulation

Bolonya declaration education

Bone marrow transplantation

Breast self examination

Bronchial asthma treatmen

Building vulnerability

Burden infectious diseases

Burnout in physicians

Cncer en mxico

Cancer survivorship research

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Capability development

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Central nervous system

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China

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Ageing – Wikipedia, the free encyclopedia

Tuesday, September 6th, 2016

Ageing, also spelled aging, is the process of becoming older. In the narrow sense, the term refers to biological ageing, especially of human beings and many animals (whereas for example bacteria, perennial plants and some simple animals are potentially immortal). In the broader sense, ageing can refer to single cells within an organism which have ceased dividing (cellular senescence) or to the population of a species (population ageing).

In humans, ageing represents the accumulation of changes in a human being over time,[1] encompassing physical, psychological, and social change. Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand. Ageing is among the greatest known risk factors for most human diseases:[2] of the roughly 150,000 people who die each day across the globe, about two thirds die from age-related causes.

The causes of ageing are unknown; current theories are assigned to the damage concept, whereby the accumulation of damage (such as DNA breaks or oxidised bases) may cause biological systems to fail, or to the programmed ageing concept, whereby internal processes (such as DNA telomere shortening) may cause ageing.

The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats has motivated research into delaying and preventing ageing.

Human beings and members of other species, especially animals, necessarily experience ageing and mortality. In contrast, many species can be considered immortal: for example, bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, and animals in the genus Hydra have a regenerative ability with which they avoid dying of old age.

Even within humans and other mortal species, there are arguably cells with the potential for immortality: cancer cells which have lost the ability to die when maintained in cell culture such as the HeLa cell line, and specific stem cells such as germ cells (producing ova and spermatozoa).[3] In artificial cloning, adult cells can be rejuvenated back to embryonic status and then used to grow a new tissue or animal without ageing.[4] Normal human cells however die after about 50 cell divisions in laboratory culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961).

After a period of near perfect renewal (in humans, between 20 and 35 years of age), ageing is characterised by the declining ability to respond to stress, increasing homeostatic imbalance and the increased risk of disease. This currently irreversible series of changes inevitably ends in death.

A number of characteristic ageing symptoms are experienced by a majority or by a significant proportion of humans during their lifetimes.

Dementia becomes more common with age.[15] About 3% of people between the ages of 6574 have dementia, 19% between 75 and 84 and nearly half of those over 85 years of age.[16] The spectrum includes mild cognitive impairment and the neurodegenerative diseases of Alzheimer's disease, cerebrovascular disease, Parkinson's disease and Lou Gehrig's disease. Furthermore, many types of memory decline with ageing, but not semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady until late adulthood[17] (see Ageing brain). Intelligence may decline with age, though the rate may vary depending on the type and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. Individual variations in rate of cognitive decline may therefore be explained in terms of people having different lengths of life.[18] There are changes to the brain: after 20 years of age there is a 10% reduction each decade in the total length of the brain's myelinated axons.[19]

Age can result in visual impairment, whereby non-verbal communication is reduced,[20] which can lead to isolation and possible depression. Macular degeneration causes vision loss and increases with age, affecting nearly 12% of those above the age of 80.[21] This degeneration is caused by systemic changes in the circulation of waste products and by growth of abnormal vessels around the retina.[22]

A distinction can be made between "proximal ageing" (age-based effects that come about because of factors in the recent past) and "distal ageing" (age-based differences that can be traced back to a cause early in person's life, such as childhood poliomyelitis).[18]

Ageing is among the greatest known risk factors for most human diseases.[2] Of the roughly 150,000 people who die each day across the globe, about two thirds100,000 per daydie from age-related causes. In industrialised nations, the proportion is higher, reaching 90%.[23][24][25]

At present, the biological basis of ageing is unknown, even in relatively simple and short-lived organisms. Less still is known about mammalian ageing, in part due to the much longer lives in even small mammals such as the mouse (around 3 years). A primary model organism for studying ageing is the nematode C. elegans, thanks to its short lifespan of 23 weeks, the ability to easily perform genetic manipulations or suppress gene activity with RNA interference, and other factors.[26] Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans.[27]

Factors that are proposed to influence biological ageing[28] fall into two main categories, programmed and damage-related. Programmed factors follow a biological timetable, perhaps a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defence responses. Damage-related factors include internal and environmental assaults to living organisms that induce cumulative damage at various levels.[29]

There are three main metabolic pathways which can influence the rate of ageing:

It is likely that most of these pathways affect ageing separately, because targeting them simultaneously leads to additive increases in lifespan.[31]

The rate of ageing varies substantially across different species, and this, to a large extent, is genetically based. For example, numerous perennial plants ranging from strawberries and potatoes to willow trees typically produce clones of themselves by vegetative reproduction and are thus potentially immortal, while annual plants such as wheat and watermelons die each year and reproduce by sexual reproduction. In 2008 it was discovered that inactivation of only two genes in the annual plant Arabidopsis thaliana leads to its conversion into a potentially immortal perennial plant.[32]

Clonal immortality apart, there are certain species whose individual lifespans stand out among Earth's life-forms, including the bristlecone pine at 5062 years[33] (however Hayflick states that the bristlecone pine has no cells older than 30 years), invertebrates like the hard clam (known as quahog in New England) at 508 years,[34] the Greenland shark at 400 years,[35] fish like the sturgeon and the rockfish, and the sea anemone[36] and lobster.[37][38] Such organisms are sometimes said to exhibit negligible senescence.[39] The genetic aspect has also been demonstrated in studies of human centenarians.

In laboratory settings, researchers have demonstrated that selected alterations in specific genes can extend lifespan quite substantially in yeast and roundworms, less so in fruit flies and less again in mice. Some of the targeted genes have homologues across species and in some cases have been associated with human longevity.[40]

Caloric restriction and exercise are two ways to activate autophagy and inhibit mTOR which can help resolve common age-related health problems.[citation needed]

Caloric restriction substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases.[80] Typically, this involves caloric intake of 6070% of what an ad libitum animal would consume, while still maintaining proper nutrient intake.[80] In rodents, this has been shown to increase lifespan by up to 50%;[81] similar effects occur for yeast and Drosophila.[80] No lifespan data exist for humans on a calorie-restricted diet,[54] but several reports support protection from age-related diseases.[82][83] Two major ongoing studies on rhesus monkeys initially revealed disparate results; while one study, by the University of Wisconsin, showed that caloric restriction does extend lifespan,[84] the second study, by the National Institute on Ageing (NIA), found no effects of caloric restriction on longevity.[85] Both studies nevertheless showed improvement in a number of health parameters. Notwithstanding the similarly low calorie intake, the diet composition differed between the two studies (notably a high sucrose content in the Wisconsin study), and the monkeys have different origins (India, China), initially suggesting that genetics and dietary composition, not merely a decrease in calories, are factors in longevity.[54] However, in a comparative analysis in 2014, the Wisconsin researchers found that the allegedly non-starved NIA control monkeys in fact are moderately underweight when compared with other monkey populations, and argued this was due to the NIA's apportioned feeding protocol in contrast to Wisconsin's truly unrestricted ad libitum feeding protocol. [86] They conclude that moderate calorie restriction rather than extreme calorie restriction is sufficient to produce the observed health and longevity benefits in the studied rhesus monkeys.[87]

In his book How and Why We Age, Hayflick says that caloric restriction may not be effective in humans, citing data from the Baltimore Longitudinal Study of Aging which shows that being thin does not favour longevity.[need quotation to verify][88] Similarly, it is sometimes claimed that moderate obesity in later life may improve survival, but newer research has identified confounding factors such as weight loss due to terminal disease. Once these factors are accounted for, the optimal body weight above age 65 corresponds to a leaner body mass index of 23 to 27.[89]

Alternatively, the benefits of dietary restriction can also be found by changing the macro nutrient profile to reduce protein intake without any changes to calorie level, resulting in similar increases in longevity.[90][91] Dietary protein restriction not only inhibits mTOR activity but also IGF-1, two mechanisms implicated in ageing.[52] Specifically, reducing leucine intake is sufficient to inhibit mTOR activity, achievable through reducing animal food consumption.[92][93]

The Mediterranean diet is credited with lowering the risk of heart disease and early death.[94][95] The major contributors to mortality risk reduction appear to be a higher consumption of vegetables, fish, fruits, nuts and monounsaturated fatty acids, i.e., olive oil.[96]

The amount of sleep has an impact on mortality. People who live the longest report sleeping for six to seven hours each night.[97][98] Lack of sleep (<5 hours) more than doubles the risk of death from cardiovascular disease, but too much sleep (>9 hours) is associated with a doubling of the risk of death, though not primarily from cardiovascular disease.[99] Sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality, though the cause is probably other factors such as depression and socioeconomic status, which would correlate statistically.[100] Sleep monitoring of hunter-gatherer tribes from Africa and from South America has shown similar sleep patterns across continents: their average sleeping duration is 6.4 hours (with a summer/winter difference of 1 hour), afternoon naps (siestas) are uncommon, and insomnia is very rare (tenfold less than in industrial societies).[101]

Physical exercise may increase life expectancy.[102] People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active.[103] Moderate levels of exercise have been correlated with preventing aging and improving quality of life by reducing inflammatory potential.[104] The majority of the benefits from exercise are achieved with around 3500 metabolic equivalent (MET) minutes per week.[105] For example, climbing stairs 10 minutes, vacuuming 15 minutes, gardening 20 minutes, running 20 minutes, and walking or bicycling for 25 minutes on a daily basis would together achieve about 3000 MET minutes a week.[105]

Avoidance of chronic stress (as opposed to acute stress) is associated with a slower loss of telomeres in most but not all studies,[106][107] and with decreased cortisol levels. A chronically high cortisol level compromises the immune system, causes cardiac damage/arterosclerosis and is associated with facial ageing, and the latter in turn is a marker for increased morbidity and mortality.[108][109] Stress can be countered by social connection, spirituality, and (for men more clearly than for women) married life, all of which are associated with longevity.[110][111][112]

The following drugs and interventions have been shown to retard or reverse the biological effects of ageing in animal models, but none has yet been proven to do so in humans.

Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.[113]

As of 2015 metformin was under study for its potential effect on slowing ageing in the worm C.elegans and the cricket.[114] Its effect on otherwise healthy humans is unknown.[114]

Rapamycin was first shown to extend lifespan in eukaryotes in 2006 by Powers et al. who showed a dose-responsive effect of rapamycin on lifespan extension in yeast cells.[115] In a 2009 study, the lifespans of mice fed rapamycin were increased between 28 and 38% from the beginning of treatment, or 9 to 14% in total increased maximum lifespan. Of particular note, the treatment began in mice aged 20 months, the equivalent of 60 human years.[116] Rapamycin has subsequently been shown to extend mouse lifespan in several separate experiments,[117][118] and is now being tested for this purpose in nonhuman primates (the marmoset monkey).[119]

Cancer geneticist Ronald A. DePinho and his colleagues published research in mice where telomerase activity was first genetically removed. Then, after the mice had prematurely aged, they restored telomerase activity by reactivating the telomerase gene. As a result, the mice were rejuvenated: Shrivelled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver, intestines and brain, recuperated from their degenerated state. "[The finding] offers the possibility that normal human ageing could be slowed by reawakening the enzyme in cells where it has stopped working" says Ronald DePinho. However, activating telomerase in humans could potentially encourage the growth of tumours.[120]

Most known genetic interventions in C. elegans increase lifespan by 1.5 to 2.5-fold. As of 2009[update], the record for lifespan extension in C. elegans is a single-gene mutation which increases adult survival by tenfold.[27] The strong conservation of some of the mechanisms of ageing discovered in model organisms imply that they may be useful in the enhancement of human survival. However, the benefits may not be proportional; longevity gains are typically greater in C. elegans than fruit flies, and greater in fruit flies than in mammals. One explanation for this is that mammals, being much longer-lived, already have many traits which promote lifespan.[27]

Some research effort is directed to slow ageing and extend healthy lifespan.[121][122][123]

The US National Institute on Aging currently funds an intervention testing programme, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice.[124] Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals and lax mouse husbandry conditions.[citation needed] The intervention testing programme aims to address this by conducting parallel experiments at three internationally recognised mouse ageing-centres, the Barshop Institute at UTHSCSA, the University of Michigan at Ann Arbor and the Jackson Laboratory.

Several companies and organisations, such as Google Calico, Human Longevity, Craig Venter, Gero,[125]SENS Research Foundation, and Science for Life Extension in Russia,[126] declared stopping or delaying ageing as their goal.

Prizes for extending lifespan and slowing ageing in mammals exist. The Methuselah Foundation offers the Mprize. Recently, the $1 Million Palo Alto Longevity Prize was launched. It is a research incentive prize to encourage teams from all over the world to compete in an all-out effort to "hack the code" that regulates our health and lifespan. It was founded by Joon Yun.[127][128][129][130][131]

Different cultures express age in different ways. The age of an adult human is commonly measured in whole years since the day of birth. Arbitrary divisions set to mark periods of life may include: juvenile (via infancy, childhood, preadolescence, adolescence), early adulthood, middle adulthood, and late adulthood. More casual terms may include "teenagers," "tweens," "twentysomething", "thirtysomething", etc. as well as "vicenarian", "tricenarian", "quadragenarian", etc.

Most legal systems define a specific age for when an individual is allowed or obliged to do particular activities. These age specifications include voting age, drinking age, age of consent, age of majority, age of criminal responsibility, marriageable age, age of candidacy, and mandatory retirement age. Admission to a movie for instance, may depend on age according to a motion picture rating system. A bus fare might be discounted for the young or old. Each nation, government and non-governmental organisation has different ways of classifying age. In other words, chronological ageing may be distinguished from "social ageing" (cultural age-expectations of how people should act as they grow older) and "biological ageing" (an organism's physical state as it ages).[132]

In a UNFPA report about ageing in the 21st century, it highlighted the need to "Develop a new rights-based culture of ageing and a change of mindset and societal attitudes towards ageing and older persons, from welfare recipients to active, contributing members of society."[133] UNFPA said that this "requires, among others, working towards the development of international human rights instruments and their translation into national laws and regulations and affirmative measures that challenge age discrimination and recognise older people as autonomous subjects."[133] Older persons make contributions to society including caregiving and volunteering. For example, "A study of Bolivian migrants who [had] moved to Spain found that 69% left their children at home, usually with grandparents. In rural China, grandparents care for 38% of children aged under five whose parents have gone to work in cities."[133]

Population ageing is the increase in the number and proportion of older people in society. Population ageing has three possible causes: migration, longer life expectancy (decreased death rate) and decreased birth rate. Ageing has a significant impact on society. Young people tend to have fewer legal privileges (if they are below the age of majority), they are more likely to push for political and social change, to develop and adopt new technologies, and to need education. Older people have different requirements from society and government, and frequently have differing values as well, such as for property and pension rights.[134]

In the 21st century, one of the most significant population trends is ageing.[135] Currently, over 11% of the world's current population are people aged 60 and older and the United Nations Population Fund (UNFPA) estimates that by 2050 that number will rise to approximately 22%.[133] Ageing has occurred due to development which has enabled better nutrition, sanitation, health care, education and economic well-being. Consequently, fertility rates have continued to decline and life expectancy have risen. Life expectancy at birth is over 80 now in 33 countries. Ageing is a "global phenomenon," that is occurring fastest in developing countries, including those with large youth populations, and poses social and economic challenges to the work which can be overcome with "the right set of policies to equip individuals, families and societies to address these challenges and to reap its benefits."[136]

As life expectancy rises and birth rates decline in developed countries, the median age rises accordingly. According to the United Nations, this process is taking place in nearly every country in the world.[137] A rising median age can have significant social and economic implications, as the workforce gets progressively older and the number of old workers and retirees grows relative to the number of young workers. Older people generally incur more health-related costs than do younger people in the workplace and can also cost more in worker's compensation and pension liabilities.[138] In most developed countries an older workforce is somewhat inevitable. In the United States for instance, the Bureau of Labor Statistics estimates that one in four American workers will be 55 or older by 2020.[138]

Among the most urgent concerns of older persons worldwide is income security. This poses challenges for governments with ageing populations to ensure investments in pension systems continues in order to provide economic independence and reduce poverty in old age. These challenges vary for developing and developed countries. UNFPA stated that, "Sustainability of these systems is of particular concern, particularly in developed countries, while social protection and old-age pension coverage remain a challenge for developing countries, where a large proportion of the labour force is found in the informal sector."[133]

The global economic crisis has increased financial pressure to ensure economic security and access to health care in old age. In order to elevate this pressure "social protection floors must be implemented in order to guarantee income security and access to essential health and social services for all older persons and provide a safety net that contributes to the postponement of disability and prevention of impoverishment in old age."[133]

It has been argued that population ageing has undermined economic development.[139] Evidence suggests that pensions, while making a difference to the well-being of older persons, also benefit entire families especially in times of crisis when there may be a shortage or loss of employment within households. A study by the Australian Government in 2003 estimated that "women between the ages of 65 and 74 years contribute A$16 billion per year in unpaid caregiving and voluntary work. Similarly, men in the same age group contributed A$10 billion per year."[133]

Due to increasing share of the elderly in the population, health care expenditures will continue to grow relative to the economy in coming decades. This has been considered as a negative phenomenon and effective strategies like labour productivity enhancement should be considered to deal with negative consequences of ageing.[140]

In the field of sociology and mental health, ageing is seen in five different views: ageing as maturity, ageing as decline, ageing as a life-cycle event, ageing as generation, and ageing as survival.[141] Positive correlates with ageing often include economics, employment, marriage, children, education, and sense of control, as well as many others. The social science of ageing includes disengagement theory, activity theory, selectivity theory, and continuity theory. Retirement, a common transition faced by the elderly, may have both positive and negative consequences.[142] As cyborgs currently are on the rise some theorists argue there is a need to develop new definitions of ageing and for instance a bio-techno-social definition of ageing has been suggested.[143]

With age inevitable biological changes occur that increase the risk of illness and disability. UNFPA states that,[136]

"A life-cycle approach to health care one that starts early, continues through the reproductive years and lasts into old age is essential for the physical and emotional well-being of older persons, and, indeed, all people. Public policies and programmes should additionally address the needs of older impoverished people who cannot afford health care."

Many societies in Western Europe and Japan have ageing populations. While the effects on society are complex, there is a concern about the impact on health care demand. The large number of suggestions in the literature for specific interventions to cope with the expected increase in demand for long-term care in ageing societies can be organised under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters.[144]

However, the annual growth in national health spending is not mainly due to increasing demand from ageing populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients.[145] A number of health problems become more prevalent as people get older. These include mental health problems as well as physical health problems, especially dementia.

It has been estimated that population ageing only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3% since 1970. In addition, certain reforms to the Medicare system in the United States decreased elderly spending on home health care by 12.5% per year between 1996 and 2000.[146]

Positive self-perception of health has been correlated with higher well-being and reduced mortality in the elderly.[147][148] Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better than that of their ill counterparts, though this link has been observed even in studies which have controlled for socioeconomic status, psychological functioning and health status.[149] This finding is generally stronger for men than women,[148] though this relationship is not universal across all studies and may only be true in some circumstances.[149]

As people age, subjective health remains relatively stable, even though objective health worsens.[150] In fact, perceived health improves with age when objective health is controlled in the equation.[151] This phenomenon is known as the "paradox of ageing." This may be a result of social comparison;[152] for instance, the older people get, the more they may consider themselves in better health than their same-aged peers.[153] Elderly people often associate their functional and physical decline with the normal ageing process.[154][155]

The concept of successful ageing can be traced back to the 1950s and was popularised in the 1980s. Traditional definitions of successful ageing have emphasised absence of physical and cognitive disabilities.[156] In their 1987 article, Rowe and Kahn characterised successful ageing as involving three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement.[157]

The ancient Greek dramatist Euripides (5th century BC) describes the multiply-headed mythological monster Hydra as having a regenerative capacity which makes it immortal, which is the historical background to the name of the biological genus Hydra. The Book of Job (c. 6th century BC) describes human lifespan as inherently limited and makes a comparison with the innate immortality that a felled tree may have when undergoing vegetative regeneration.[158]

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Longevity Genes Project | Institute for Aging Research …

Monday, August 15th, 2016

Nir Barzilai, M.D. Director of the Institute for Aging

Research Director of the Nathan Shock Center of Excellence in the Basic Biology of Aging

Ingeborg and Ira Leon Rennert Chair of Aging Research

Dr. Barzilai's bio / cv

Watch video

Request an Interview with Dr. Barzilai

Watch Dr. Barzilai in The Healthspan Imperative

The Longevity Genes Project

What if people could live to be 100 and beyond and still be healthy, active and engaged?

What if there were a way to age without a slow and painful decline?

In the Longevity Genes Project at Albert Einstein College of Medicine, Dr. Nir Barzilai and his team conducted genetic research on more than 500 healthy elderly people between the ages of 95 and 112 and on their children.

The identification of longevity genes by Einstein researchers could lead to new drug therapies that might help people live longer, healthier lives and avoid or significantly delay age-related diseases such as Alzheimer's disease, type 2 diabetes and cardiovascular disease.

The Longevity Genes Project Video Series

This video series includes informative interviews with Dr. Nir Barzilai, who leads the Einstein longevity research efforts, and with four study participants whose diverse and compelling stories will inspire you. We invite you to view all of the videos and leave comments. Click on the links below to view each segment.

Research: Dr. Nir Barzilai

Personal Profiles: Lilly Port: Age 96 | Harold Laufman: Age 98 | Irma Daniel: Age 103 | Irving Kahn: Age 104

Longevity and Longenity Information and preliminary results of Einstein's search for longevity genes in the Jewish Ashkenazi population and genotypes and phenotypes for exceptional longevity.

Why Ashkenazi Jews? Information about the "founder effect" and the historically unique Ashkenazi Jewish population.

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Longevity Genes Project | Institute for Aging Research ...

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Genetic Secrets Of Longevity Discovered | IFLScience

Saturday, August 13th, 2016

Whats the secret to living longer? Scientists have been pondering this for some time now and while we understand that various lifestyle and environmental factors contribute to our longevity, it is also evident that genetics plays a role. In fact, family studies have indicated that genetic factors account for around 20-30% of the variation in adult lifespan. So what are these genetic secrets to longevity? A new study, published in Aging Cell, may have some answers.

Previous work identified a couple of candidate genes that researchers suspect may play a role in longevity. The genes identified were apolipoprotein E (APOE), which transports cholesterol around the body, and FOXO3A which may affect insulin sensitivity. Variations in these genes were found to be associated with longevity; however, neither had a large influence, which left scientists suspecting that there must be other factors at play.

To find out more, researchers from the Spanish National Cancer Research Center scoured the protein-coding genes, or exomes, of members of three separate families that all had exceptionally long-lived members. Three of the individuals sequenced lived to be 103 or older, and their siblings lived to be 97 or older. They then compared these with sequence data from 800 other people that acted as controls.

They found that rare variants in one particular gene cropped up in all three familiesapolipoprotein B (APOB). Like the APOE protein, APOB is a cholesterol transporter. APOB helps to carry bad cholesterol, or low-density lipoprotein (LDL), in the blood. While our bodies need cholesterol, LDL has a bad rep because it can build up along the walls of blood vessels, blocking arteries and eventually leading to heart attacks in some.

Its possible that these genetic variations reduce the levels of LDL in the blood, an idea that the researchers are now investigating. According to lead author Timothy Cash, if the long-lived individuals do have lower cholesterol levels, it would reinforce the idea that cardiovascular health is an important factor in the aging process. Interestingly, variations in APOE are also known risk factors for cardiovascular disease, which is likely due to elevated lipid levels.

[ViaNew ScientistandAging Cell]

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Genetic Secrets Of Longevity Discovered | IFLScience

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Genetics of longevity and aging.

Saturday, August 13th, 2016

Longevity, i.e., the property of being long-lived, has its natural limitation in the aging process. Longevity has a strong genetic component, as has become apparent from studies with a variety of organisms, from yeast to humans. Genetic screening efforts with invertebrates have unraveled multiple genetic pathways that suggest longevity is promoted through the manipulation of metabolism and the resistance to oxidative stress. To some extent, these same mechanisms appear to act in mammals also, despite considerable divergence during evolution. Thus far, evidence from population-based studies with humans suggests the importance of genes involved in cardiovascular disease as important determinants of longevity. The challenge is to test if the candidate longevity genes that have emerged from studies with model organisms exhibit genetic variation for life span in human populations. Future investigations are likely to involve large-scale case-control studies, in which large numbers of genes, corresponding to entire gene functional modules, will be assessed for all possible sequence variation and associated with detailed phenotypic information on each individual over extended periods of time. This should eventually unravel the genetic factors that contribute to each particular aging phenotype.

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Genetics of longevity and aging.

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The Okinawa Centenarian Study : Evidence based gerontology

Thursday, August 4th, 2016

Evidence-Based Gerontology

One of the most important things about the Okinawa Centenarian Study is the fact that it is based on solid evidence. The most important evidence needed for any centenarian study is reliable age-verification data. Throughout Japan (including Okinawa prefecture), every city, town, and village records birth, marriage and death data (among other data) in a koseki (family register). This system was instituted throughout Japan in the 1870's. The koseki is supplemented by a regular census undertaken every five years. Life tables calculated from this database show one of the world's longest life expectancies and prevalence data show the world's highest known concentration of centenarians for any country or state.

After examining over 900 Okinawan centenarians and numerous other elderly in their seventies, eighties, and nineties, some fascinating findings have emerged. One, genetic factors appear important to human longevity, including Okinawan longevity. Two, it has also become clear that the Okinawan lifestyle provides many reasons why older Okinawans are so remarkably healthy so far into their senior years. Discovering the reasons for the apparent genetic and environmental advantages could have an important impact on our health and well-being in the West. Below appear some of the key findings and what they mean in terms of healthy aging -- for the Okinawans, and the rest of us.

Identifying factors that help us remain healthy, vigorous and disability-free at older ages is one of our major research priorities. Since the completion of the Human Genome Project and the HapMap Project (a project to identify common variations in human genes), a promising novel strategy by some human longevity researchers is to try to identify genes (and variations of those genes) that impact human aging and longevity. If such genes and their genetic pathways can be identified then novel therapies might be created that affect the biology of these pathways. This may help prevent or treat age-associated diseases and perhaps even slow aging itself. Such therapies might include interventions as simple as diet and focused exercise, specific food compounds, neutraceuticals or pharmaceuticals.

How much of human longevity is due to genes? Estimates of the heritability of human lifespan vary from 10-50% with the most common finding being that about a third of human lifespan may be heritable. Phenotypes that suggest slower aging, such as survival to 90+ years, may have an even stronger genetic basis, which explains why centenarians and near-centenarians tend to cluster in families. But until the discovery of the apolipoprotein E (ApoE) gene, there was little evidence for a single gene effect large enough to impact human longevity. This discovery has been replicated in many populations, suggests that associations with some genes are large.

Studies of long-lived humans, such as American centenarians, have helped identify other promising genetic loci for longevity and healthy aging. However, these studies are often limited in scope due to small sample sizes, genetic admixture, and inappropriate selection of controls. Some success has been achieved through use of genetically homogeneous populations with smaller gene pools.

Our research group was the first to identify so called "human longevity genes" using centenarians as a study model when we published a study showing that Okinawan centenarians have HLA (human leukocyte antigen) genetic polymorphisms that place them at lower risk for inflammatory and autoimmune diseases (see figure below: Takata et al., Lancet 1987).

We also studied the mortality patterns of centenarian siblings. Past family studies in other populations have shown that there are familial (genetic) components to longevity. That is, longevity tends to run in families. In support of this, we found that a mortality advantage exists for centenarian siblings versus their age-matched birth cohorts. This advantage appears sustained over the course of the siblings' lives. At each 5-year age interval until age 90 years, siblings of Okinawan centenarians maintained approximately a 50% lower mortality risk. This resulted in an average of 11.8 years extra lifespan compared to their age-matched birth cohort. The sustained mortality advantage over the life course provides further evidence that human longevity has an important genetic component since most environmental mortality advantages, such as education, diminish or disappear completely in older age groups (see figure below from Willcox BJ et al. Siblings of Okinawan centenarians exhibit lifelong mortality advantages. J Gerontol A Biol Sci Med Sci. 2006;61:345-54).

In order to quantify the genetic contribution to Okinawan longevity, we studied the sibling recurrence risk ratio or "lambda of sib (ls)" in siblings of Okinawan centenarians. This is a calculation that has been shown to give a rough idea of how important genes might be to a given phenotype, such as a disease, or even to something more complex like human longevity.

We analyzed a population-based sample of 348 Okinawan centenarians (born between 1874 and 1902) and 969 of their siblings (507 females and 462 males) to explore the feasibility of a genome-wide study of Okinawan longevity. The ls for Okinawan centenarians was 6.5 (95% confidence interval: 3.9-10.7) for females and 5.1 (95% confidence interval: 1.8-14.2) for males, respectively. The weighted sex-combined ls was 6.3. These estimates in Okinawans appear to be higher than those obtained in past work on U.S. Caucasians. For example, a study of the familial component of longevity in Utah families estimated the ls to be 2.3. This suggests an important genetic component to Okinawan longevity and supports further work on the genetics of healthy aging and longevity in this population (see Willcox BJ et al., Substantial advantage for longevity in siblings of Okinawan centenarians. Genetic Epidemiology). 2005;29:286.

Does this mean that Okinawan longevity is all genetic? Not at all. We believe the Okinawans have both genetic and non-genetic longevity advantages -- the best combination. In fact, we have written extensively that the Okinawan traditional way of life -- the dietary habits, the physical activity, the psychological and social aspects, all play an important role in Okinawan longevity.

While most studies of humans have suggested that about a third of human longevity is due to genetics, this depends on the age, sex, ethnicity and environment of the study population. For example, studies of "model organisms" of aging, such as rodents, who share many of the same genes as humans, have shown that single genes can influence lifespan by 50% or more. On the other hand, studies of lifestyle interventions, such as eating fewer calories (a.k.a. "caloric restriction") have shown that this dietary intervention can also yield increases in lifespan of a similar magnitude (see Willcox DC et al., Caloric restriction and human longevity: what can we learn from the Okinawans? Biogerontology. 2006;7:173-77). The key is to study both genetic and non-genetic (environmental) factors and ultimately "gene-environment" interactions that lead to healthy longevity.

One of the most durable theories of aging is the free radical theory. This theory postulates that damage from free radicals (unstable molecules), generated mainly from metabolizing food into energy, ultimately damages vital body molecules (tissue, DNA, etc.). This damage accumulates with time until, like an old car, we fall apart. In support of this theory, one of the most important findings in free-radical research has been that eating fewer calories increases life span (Sohal RS, et al. Science 1996;273:59-63; Heilbronn LK, et al. Am J Clin Nutr 2003;78:361-9). The initial evidence that this may work in humans has been indirect and based on observation of the low caloric intake of the Okinawans and their long life expectancy (Willcox DC, et al. Biogerontology 2006). More direct evidence suggests that Okinawans following the traditional ways have low blood levels of free radicals. The elders had significantly lower levels of lipid peroxide-compelling evidence that they suffer less free-radical-induced damage. This may indicate healthier lifestyles but may also be due to gene variants that result in lower blood levels of free radicals. This is currently under investigation.

Levels of Lipid Peroxides in Okinawan Centenarians and Septuagenarians

Elderly Okinawans were found to have impressively young, clean arteries, low cholesterol, and low homocysteine levels when compared to Westerners. These factors help reduce their risk for coronary heart disease by up to 80% and keep stroke levels low.

Their healthy arteries appear to be in large part due to their lifestyle: diet, regular exercise, moderate alcohol use, avoidance of smoking, blood pressure control, and a stress-minimizing psychospiritual outlook. However, there are also potential genetic aspects such as lower fibrinogen levels possibly due to differences in fibrinogen-related genes. A recent autopsy study that we conducted on a centenarian demonstrated that her coronary arteries were virtually free of atherosclerotic plague (Bernstein, Willcox et al. JGMS 2004).

The chart to the right indicates that the higher the plasma homocysteine (a new risk factor) level is, the more people suffer from cardiovascular disease. Homocysteine is an amino acid that causes damage to arterial walls. It is higher in people who don't get enough folate (e.g. green leafy vegetables) and vitamins B6, B12 but low in Okinawans.

Okinawans are at extremely low risk for hormone-dependent cancers including cancers of the breast, prostate, ovaries, and colon. Compared to North Americans, they have 80% less breast cancer and prostate cancer, and less than half the ovarian and colon cancers. Some of the most important factors that may protect against those cancers include low caloric intake, high vegetables/fruits consumption, higher intake of good fats (omega-3, mono-unsaturated fat), high fiber diet, high flavonoid intake, low body fat level, and high level of physical activity.

Hormone-Dependent Cancer Risk

Yearly Cancer Deaths (per 100,000 people)

Adapted from World Health Organization 1996; Japan Ministry of Health and Welfare 1996

NK, a typical healthy centenarian was reported to be in particularly good health, completely independent, and still farming. He is shown here getting his bone density tested by heel bone ultrasound.

Okinawans have about 20% fewer hip fractures than do mainland Japanese, and Japanese have about 40% fewer hip fractures than Americans (Ross PD, et al. Am J Epidemiol 1991;133:801-9). Our research on Okinawan elders showed that their bone density, when adjusted for body size, is similar to Americans, and like the rest of us they continue to lose bone mass as they get older, but possibly at a slower rate. We compared bone mineral density in a group of Okinawans to two groups from mainland Japan and found that by age forty for women and age fifty for men the groups began to diverge. The Japanese began to lose significantly more calcium from their bones than the Okinawans, suggesting the Okinawans preserve their bone density at healthy levels for longer periods of time than other Japanese (Suzuki M, et al. Japanese J Bone Res 1995;63:166-72). Protective lifestyle factors that may play a role here include high calcium intake by Okinawans in both food and their natural drinking water, high vitamin D levels from exposure to sunlight, increased physical activity, especially at older ages, and high intake of dietary flavonoids (estrogenic compounds from plant foods).

Prevalence surveys suggest that the dementia rate is fairly low among the Okinawan elderly, compared to other elderly populations. Even into their late 90s Okinawans suffered lower dementia rates than reported for comparable populations in the United States and elsewhere.

Photo: 97 year old karate master Seikichi Uehara

Okinawan centenarians have been lean throughout their extraordinarily long lives, with an average body mass index (BMI) that ranged from 18 to 22 (lean is less than 23). The Okinawans have traditionally kept eating a low-calorie, low glycemic load diet, practicing calorie control in a cultural habit known as hara hachi bu (only eating until they are 80% full), and keeping physically active the natural way. Particular exercise interventions are under study for their role in healthy aging.

Women's health and aging is one of our research interests. For example, women in Okinawa tend to experience menopause naturally and nonpharmacologically with fewer complications such as hot flashes, hip fractures, or coronary heart disease. Lifestyle determinants include diet, avoidance of smoking and exercise in the form of dance, soft martial arts, walking and gardening. Okinawan women also have a very high intake of natural estrogens through their diet, mainly from the large quantities of soy they consume. Soy contains phytoestrogens, or plant estrogens called flavonoids. The other important major phytoestrogens are lignans, which are derived from flax and other grains. All plants, especially legumes (beans, peas), onions, and broccoli, contain these natural estrogens, but not nearly in the same quantity as soy and flax. Recent double-blind placebo controlled studies support the ability of soy isoflavones to slow the bone loss (Alekel D, et al. Am J Clin Nutr 2001;72:844-52) and hot flashes (Albertazzi P, et al. Obstet Gynecol 1998;91:6-11) that occur with menopause.

Okinawan elders may have higher levels of sex hormones, including natural DHEA, estrogen, and testosterone than similarly aged Americans, suggesting that the Okinawans are physiologically younger. DHEA is a steroid produced in the human adrenal gland, and some studies suggest that it may help ameliorate the ravages of aging. However, taking DHEA supplements could increase risk for breast and other cancers so we do not recommend taking DHEA supplements. More supported by the scientific literature is that DHEA levels decline in direct ratio with age, so it may be a good marker of biological age. Okinawans appear to have higher DHEA levels than similarly aged Americans suggesting that Okinawans may age slower than Americans. As Okinawans age, both sexes maintain remarkably higher levels of estrogen which may help protect against heart disease and osteoporosis. Testosterone is the male equivalent of estrogen. Higher endogenous levels increase our muscle mass and our body hair, deepen our voices, and control our libidos, among other functions. This hormone also appears higher in older Okinawan men. Cross-national population studies are needed to confirm these differences and their biological significance.

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Can Humans Live Forever? Longevity Research Suggests …

Thursday, August 4th, 2016

Scientists may be able to make substantial gains in extending not only the length of human life, but the quality of life as we age, according to many researchers. That won't be limited to breakthroughs in the laboratory. To a significant extent, it will depend on how we live our lives.

As for the scientists, first they have to answer a very basic question. Why do humans live longer than any other mammals?

For starters, we are big. Long ago scientists recognized a relationship between body size and longevity. Humans just narrowly edge out the elephant (so size isn't the whole story) to win the Olympic gold for living longer, but recent research reveals that's just part of the story.

We also have huge brains compared to the size of our bodies. We are mobile, have few predators except for other humans, and there's a drugstore on every corner.

It wasn't always that way. During most of recorded history any human who reached the mid thirties had beaten the system. Over the past century we gained a global average of 30 years, about 25 of which are attributed to improvements in public health, according to federal statistics.

Today, the global life expectancy is 67.2 years. It's around 78 years in the United States, and a few years more in Japan, the world leader for sticking around.

Genetics, of course, play a key role in longevity. In recent years, when we entered the golden age of genetics, many hoped to discover the "longevity gene" that allowed an increasing number of humans to live more than a century. For awhile, they thought they had found it.

One gene produces sirtuins, a protein thought to increase lifespan in several organisms, and that protein quickly became the darling of producers of anti-aging creams. But last year an international team of researchers found that sirtuins have no effect on animal longevity.

That came as no surprise to scientists at the University of California, San Francisco, who had determined that there is no longevity gene. As has often been the case in genetics in recent years, it's much more complicated than that.

It turns out that there are many genes that affect lifespan, but each of those genes has a very limited role. The San Francisco researchers found that some genes make proteins that fight bacterial infections, while others ward off oxidative stress and protein damage, commonly associated with aging. But all these genes don't just do their own thing. They are apparently controlled by at least two other genes that act as drill sergeants. Research by these scientists found that when all these genes work right, the lifespan of the roundworm, C. elegans, doubled. That worm is used in much research because it is a simple organism that shares many genes with humans.

But will the same thing work for humans? Maybe.

In a related study, scientists at the University of Liverpool reported earlier this year that some proteins change over time in long living species, including humans. Joao Pedro Magalhaes and his colleagues studied 30 mammals and found that these proteins evolve during the course of the lifetime "to cope with biological processes impacted by aging, such as DNA damage." In other words, animals that live longer are better equipped to make repairs in tissues and organs that help them fight the aging process.

There is a huge body of evidence showing that size really does matter, both in terms of body mass and cerebral tissue. Researchers in Barcelona studied 493 mammal species and found that a larger brain leads to a longer life.

A smarter animal is better equipped to deal with environmental challenges and less likely to take silly chances, like picking a fight with a much bigger animal. That may seem obvious, but it's less clear why body size should contribute to longer lifespan. Among mammals, the top four are humans, followed by elephants, horses and hippopotamuses, but most likely the hippo wouldn't score all that high on an IQ test.

The turkey buzzard tops the list for birds at 118 years, maybe because it's smart enough to wait for road kill instead of attacking a live animal.

But the giant tortoise is the real champ. The world mourned the passing of Lonesome George in the Galapagos Islands earlier this year. The actual age of old George is unknown, although it's clear he made it well past the century mark. Among the superachievers was Tu'I Malila, who was presented to the royal family of Tonga by Capt. James Cook in 1777. He was thought to be 188 when he died in 1965. That still leaves the question of why size matters. Adrian Bejan, a mechanical engineering professor at Duke University, has spent years studying the relationship between size and lifespan, and he is out with a new idea.

Bejan argues in a paper published this week in Nature Scientific Reports that big animals live longer because they travel farther, thus giving them access to more resources. Mobility is the key. Get off the couch.

If he's right, then that leaves longevity largely in our own hands. Do the right thing and you'll live longer. Physicians tell us that all the time. Don't smoke. Get plenty of exercise. Eat right. Researchers at Newcastle University in England think they have figured out why something like eating a low calorie diet can increase lifespan. Aging is strongly influenced by senescence, the end of a cell's ability to replicate itself. They fed mice a low calorie diet and the accumulation of senescent cells plummeted, thus defeating much of the aging process.

It worked even for older mice, suggesting that eating less or at least fewer calories may be our best defense against aging and an early death.

No more ice cream? I'm waiting for a magic pill.

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Aging, genetics and longevity drugs – biopsychiatry.com

Thursday, August 4th, 2016

BOSTON, Massachusetts (AP) -- A young man climbs from bed, stares into a mirror and glimpses his future.

He has just turned 34. His body is trim, his hair thick and dark. But what's that around his eyes? Those crow's-feet are getting harder to ignore. And do his teeth look a bit ground down by decades of chewing, or is it his imagination?

He will probably repeat the same check tomorrow, and tomorrow, and tomorrow -- about 16,000 more times if he, like the average American, dies at around 80. "I don't think 80 years is long enough. There's a lot of things I want to do," he laments.

But what can he -- or anyone -- do about getting old? He can't stop it, any more than he can dispel rain clouds roiling on the horizon, any more than ancient alchemists could distill a real elixir of immortality.

Or can he?

His name is David Sinclair. He is biologist at Harvard Medical School. His job is to prevent aging.

Catapulted by advances in biotechnology, scores of researchers have begun to pinpoint genes that may prolong human life while delaying its late-stage diseases, frailties and maybe even gray hair and wrinkles. Their remarkable successes in laboratory animals -- like worms that live four times longer than normal -- have already germinated several drug companies. They hope to develop compounds to stretch healthy lifetimes beyond limits once presumed to be fixed.

Some respected researchers envision millions living as long as Jeanne Calment of France, who died at age 122 in 1997. Tom Johnson, a University of Colorado geneticist, thinks people could one day live to 350 years old, spanning the ages like Methuselah and the other biblical patriarchs.

"I am absolutely convinced we are going to be able to extend human life," Johnson says. "This is not science fiction."

Under the best circumstances, a life-prolonging drug could conceivably arise in five years, says longevity guru Cynthia Kenyon, a molecular geneticist at the University of California-San Francisco.

While enthusiastic about distant prospects, some others predict only modest advances for the near future, because aging is such a fundamental and complex process. "I think it would be sensationalist and crazy to think we'd be seeing people living to 120, 130," argues Thomas Perls, a Boston University aging specialist who studies the genetics of centenarians.

In truth, no one knows for sure what can be accomplished or how soon. However, for the first time in human history, an intense and methodical quest is under way to turn off aging with proven science, instead of snake oil.

For centuries, aging has been understood as a scattered, chaotic, inevitable breakdown of the body and its organs. Like a car with too many miles, it eventually wears out. You can keep fixing parts, but others soon break down.

There was special reason for doubt in the genetic approach to slowing aging. Evolutionary theory dictates that we inherited genes that most helped our ancestors reach sexual maturity, not ones that helped or hurt them afterward.

If so, a genetic trigger for aging would be a long shot, except for one thing.

At first, it was more of a biological curiosity. In the 1930s, Cornell University nutritionist Clive McCay discovered that underfed rats live a lot longer than others. Just cut calories by about 30 percent, balance their diet, and they survive about 40 percent longer or more. The technique works in fish, fleas, and other species, and early data suggest it works in monkeys too, say researchers at the University of Wisconsin and the National Institute of Aging.

Underfeeding has revealed a second remarkable power: It keeps animals healthy, largely free of aging ailments like cancer and heart disease. They stay strong and energetic. They even keep more fur.

"On one side, the calorie-restricted mice are jumping, and running around, and looking young," says Stephen Spindler, a biochemist who does such experiments at the University of California-Riverside. "On the other side, the litter mates look old. They're gray, and they have more balding. They move less. It makes me want to go on a diet."

Even if it proved to work in people -- still an open question -- few would likely tolerate such a Spartan diet.

Maybe dieting isn't necessary, though. Researchers suspected that the effects of underfeeding point to some built-in biological switch after all: a set of master genes that can delay aging. Could they be found? And could their effect be mimicked by a drug that boosts or blocks the right proteins, the soldier molecules that do the work assigned by genes?

Kenyon, of the University of California-San Francisco, knew of a microscopic roundworm that, when starved or overcrowded, slips into suspended animation. In this hardened condition known as dauer, it can hold out for months. It would otherwise die within about three weeks.

This state is directed by a gene, daf-2, that controls growth by helping manufacture an insulin-like hormone. Kenyon wondered if worms with disabled variants of this gene might turn into spry, wiggly Methuselahs. In her tests, they did. Similar manipulations worked in flies and mice. A raft of such discoveries in the 1990s helped legitimize the new field of aging genetics.

"Aging had been cast kind of into the trash heap of biology, particularly in molecular terms. There's nothing much you can do about it, so what's the point?" says Kenyon, a 40-something dynamo who talks in a teenager's rapid-fire bursts and gives her age as 150.

Over the past 15 years, researchers have discovered several dozen genes that prolong life significantly in yeast, roundworms, fruit flies and mice. As in underfed animals, they appear to put off not just death, but the hobbling conditions of old age.

Most of these genes carry deadpan scientific monikers: p66shc, ctl-1, Lamin A. Others were mercifully christened in whimsy like age-1, clock, Methuselah, and INDY -- for "I'm Not Dead Yet," a name inspired by a line from a Monty Python movie.

Many longevity genes first tracked in animals have human counterparts. Other genes were first spotted in humans.

Nerve researcher Gabrielle Boulianne, of the University of Toronto, was studying one of them in 1998. She was researching amyotrophic lateral sclerosis, the degenerative nerve condition known as Lou Gehrig's disease. It had been linked to a gene known as SOD1, which treats metabolic waste products. Since fruit flies carry a twin gene, she transplanted and supercharged the human gene in their nerve cells, hoping to develop a research model for the disease.

What happened next was unforeseen: The flies lived an average of up to 40 percent longer. "In some respects, I was shocked," Boulianne says. "That was not the original goal."

In keeping with underfeeding experiments, some of these genes help resist environmental threats, like food shortages, overheating or infection. Some slow down metabolism or boost its efficiency. Others help recondition the body's protein building blocks or reduce the destruction of gene-degrading free radicals. Still others make hormones that control growth and cell division, a process that goes awry in cancer.

Many of these genes, like gatekeepers, open or close access to other genes. At the Massachusetts Institute of Technology, Lenny Guarente -- Sinclair's mentor -- is pursuing a gatekeeper gene common to mice and humans, SIRT1. It is tied to several players implicated in aging: sugar metabolism, hormone signaling, and cellular death.

In theory, such genes can block the chemical messengers that spur aging ailments like cancer, heart disease and Alzheimer's. These researchers dream of one pill that fits all.

"It's a new way in thinking about diseases," says Guarente, a lanky 51-year-old with an impish smile who looks like he may have already found an aging secret and tried it.

Elixir Pharmaceuticals, which he co-founded in Cambridge, Massachusetts, plans to test several drugs in animals. Since its early days in 2001, it has raised $36.5 million and grown to a staff of about 30, according to CEO Edward Cannon.

He acknowledges it's still unclear how to move a longevity drug to market. Given even the paltry human life span now, the thorough testing required by the U.S. Food and Drug Administration would take too long. Cannon says the first longevity drugs might be approved for specific diseases of aging, but prescribed more broadly by some doctors to prolong life.

"It's a great business opportunity," says Xi Zhao-Wilson, CEO of a competitor, Biomarker Pharmaceuticals in Campbell, California. "The market is huge, we know that."

Some executives say their longevity products might be marketed first for pets or as human dietary supplements, allowing makers to skirt full-blown human testing. It's a market where claims are sometimes made on shaky grounds, but the longevity companies say their products would be based on solid science.

Some biologists worry that likely side effects are being undersold already. They say that nearly any drug that alters the workings of a powerful master gene will probably stir up unintended effects. They warn of infertility, sluggish metabolism or weakened immunity.

Longevity researcher Steven Austad at the University of Idaho says all aging genes found so far would do harm "not necessarily apparent in the laboratory."

Yet he felt confident enough to bet a colleague $150, on a lark, that someone born by 2000 will be alive and well in the year 2150. Assuming that person wouldn't be either of them, the two scientists banked their combined $300 to pay the winner's descendants when the bet is decided.

By then, the pot is estimated at $500 million, thanks to something that only gets better with time: compound interest.

Taking Austad's bet was sociologist S. Jay Olshansky, an authority on aging demographics at the University of Illinois-Chicago. "You get many of these gene jockeys grossly exaggerating and extending the work done on invertebrates and other organisms to ... humans," he says. But even he holds great hope for the field in the long run.

Some scientists and scholars say it's already time to start considering how to handle the profound impact long-life drugs would have on society. Will they tack on extra years of sickness to the bonus years of health, overwhelming the medical system? Can society create enough jobs for older workers and support retirees longer?

Political scientist Francis Fukuyama, on The President's Council on Bioethics, says such problems beg for discussion because a proven longevity drug would be "almost impossible to stop."

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Longevity, how to live longer with diet, food, and dietary …

Thursday, August 4th, 2016

Longevity Secrets, practical steps to take to have a longer life, diet, food and supplements Subscribe to a FREE Natural Healing newsletter at Physician Formulas December 15, 2015 by Ray Sahelian, M.D.

In the USA, the two major risk factors for premature death are smoking and high blood pressure. Even in middle age, adopting a healthy lifestyle can lower the risk for heart disease and premature death. A program of healthy eating, exercise and stress reduction can not only reverse some diseases -- it may actually slow down the aging process at the genetic level. The lifestyle changes affected the telomeres -- little caps on the end of the chromosomes that carry the DNA, a team at the University of California, San Francisco reported in December 2013.

Supplements for Longevity and healthier life There is currently no evidence in humans that taking supplements or hormones (such as human growth hormone) will make us live longer. However, it seems reasonably safe to take small amounts of certain supplements that have shown in preliminary research to be helpful.

Antioxidants People think that a longevity secret is to take as many antioxidants in high doses. But more is not necessarily better. If you plan to take them, use low doses, even it means taking a portion of a capsule. Acetyl l-carnitine and the antioxidant lipoic Acid are interesting nutrients that may be beneficial, more research is needed before making recommendations. Acetylcysteine could be of benefit. Carnosine appears to be able to extend the lifespan of cultured cells, and rejuvenate senescent cells. Resveratrol from red wine has potential. Eat a few grapes a week or drink a couple of ounces of wine a few times a week. Wine has many beneficial polyphenols. The compound that makes red wine a healthful drink may also hold one of the secrets to longevity. Researchers found that resveratrol acted on fruit flies and worms in the same way as a method known to extend longevity of animals including monkeys -- sharply restricting how much they eat.. The finding opens the possibility that people could take a pill to achieve the same benefits as strict dieting to live longer, healthier lives, said David Sinclair of Harvard Medical School in Boston, who led the study. "We found this chemical that can extend longevity of every organism we give it to." Royal Jelly has been studied in rodents. Vitamin D supplementation may improve longevity in those who have a low intake of vitamin D.

Nutritional supplements help mice stay healthy with age When mice were supplemented with more than 2 dozen vitamins, minerals nutrients and herbal extracts, they did not experience a 50 per cent loss in daily movement like other non-supplemented animals. The benefits were associated with an improvement in the activity of mitochondria as well as by reducing levels of free radicals. David Rollo, from McMaster University, says, This study obtained a truly remarkable extension of physical function in old mice, far greater than the respectable extension of longevity that we previous documented. This holds great promise for extending the quality of life of health span of humans. David Rollo says that it is unclear if the effects would be repeated in humans and years or decades of clinical trials would be required before any definitive conclusions could be made. The dietary product given to the mice included vitamins B1, B3 (niacin), B6, B12, C, D, E, folic acid, beta-carotene, CoQ10, rutin, bioflavonoids, ginko biloba, ginseng, green tea extract, ginger root extract, garlic, L-Glutathione, magnesium, selenium, potassium, manganese, chromium picolinate, acetyl L-carnitine, melatonin, alpha-lipoic acid, N-acetyl cysteine, acetylsalicylic acid, cod liver oil, and flax seed oil. Dietary amelioration of locomotor, neurotransmitter and mitochondrial aging. Experimental Biology and Medicine 2010.

Longevity enhancers - Secrets and simple steps to take: The field of longevity and anti-aging is full of promises and unsubstantiated claims. As of now, there is no definitive research in humans of any substances or techniques that have been proven to extend longevity. However, there are a number of steps we can take to potentially live longer. These include:

1. Positive Attitude Have a positive attitude and improve your coping skills to daily stress. Embrace the philosophy that "It's not what happens to me, it's what I make of it." In a sample of people aged 50 and older who were followed for an average of 23 years, respondents who reported having a positive attitude toward aging lived an average of more than 7 years longer than those who had a more dismal view of getting older. Do you want to be happier? Take a look at my book on Happiness. A 50-year long study suggests that longevity is improved in men and women who are active, emotionally calm, and organized. Psychosomatic Medicine, July / August 2008. Optimists live longer, healthier lives than pessimists. Researchers at University of Pittsburgh, led Dr. Hilary Tindle, looked at rates of death and chronic health conditions among participants of the Women's Health Initiative study, which has followed more than 100,000 women ages 50 and over since 1994. Women who were optimistic were 14 percent less likely to die from any cause than pessimists and 30 percent less likely to die from heart disease after eight years of follow up in the study. Optimists also were also less likely to have high blood pressure, diabetes or smoke cigarettes. March 2009. Emotionally stable, intelligent men may live longer than neurotic, less intelligent men. Men with neurotic traits -- a tendency to worry and to experience emotional ups and downs -- and lower cognitive ability have a higher mortality rate than men without these traits. Psychosomatic Medicine, 2009. If you feel like you have most things in your life under control, this could make you feel even more confident and you'll probably live longer than other people. Feb. 3, 2014, Health Psychology, online.

People with a bright outlook on the future may live longer than those who take a dimmer view. Researchers in the Netherlands found that older men and women judged to have optimistic personalities were less likely to die over the nine-year study period than those with pessimistic dispositions. Much of this reduced risk was due to lower rates of death from cardiovascular disease among the most optimistic men and women in the study. They were 77 percent less likely to die of a heart attack, stroke or other cardiovascular cause than the most pessimistic group-regardless of factors such as age, weight, smoking and whether they had cardiovascular or other chronic diseases at the study's start. 2. Keep a normal weight Keep a healthy weight and reduce the number of calories consumed, but not to the point of starving. Caloric restriction prolongs life in animals, but less is known in humans. Cutting calories may do more than help people shed excess weight. According to a new report, a low-calorie diet may also slow age-related changes in the heart's genes that can lead to chronic disease. In the study, "middle-aged" 14-month-old mice were fed either a normal diet or one restricted in calories. When the mice reached 30 months of age, or the equivalent of 90 years of a human life span, the researchers analyzed their heart tissue. The hearts of mice on the low-calorie diets showed nearly 20% fewer age-related genetic changes and also appeared to have less DNA damage than those of mice on regular diets. Restricting calories also inhibited potentially disease-causing changes in the immune system, and suppressed apoptosis, or programmed cell death. A telephone poll conducted by ABC News found that 73% of respondents would not restrict their caloric intake in order to live longer. Mouse study: eating less at any age prolongs life. Bottom line: reduce caloric intake, but not to the point of having a miserable time. The size of an aging man's belly and the bulk of his biceps provide a more accurate picture of his mortality risk than body mass index (BMI) alone. As people age they typically lose muscle mass and gain belly fat.

3. What you eat determines how long you live Consume a healthy diet. Reduce consumption of foods cooked at high temperature. Drink more tea, particularly green tea. By relying more on steaming, boiling and stewing to cook foods and using acidic marinades on meat cooked with dry heat, people may be able to stay healthier. These strategies will reduce the amount of advanced glycation end products (AGEs), or glycotoxins that people consume with their food. The more AGEs healthy people eat, the greater their levels of inflammation and oxidative stress. Use the sugar substitute stevia which contains stevioside, a safe sweetener with no calories. Make sure to have more long chained fatty acids in your diet such as omega-3 fatty acids found in fish. Fresh fruit and vegetable consumption of greater than 5 servings a day is associated with progressively longer survival and lower mortality rates. 2013 American Society for Nutrition. Fruit and vegetable consumption and all-cause mortality: a dose-response analysis.

Duke Med Health News. 2013. Vegetarian diets aid longevity, reduce risk of all-cause mortality. But results are more significant in men than women. Further research is needed to determine why.

High total red meat consumption was associated with progressively shorter survival, largely because of the consumption of processed red meat. Consumption of nonprocessed red meat alone was not associated with shorter survival. Differences in survival associated with processed and with nonprocessed red meat consumption. Am J Clin Nutr 2014.

Herbs and spices Consume more culinary herbs and spices such as garlic, onion, curcumin, parsley, mint, and others.

4. Exercise and longevityRegular exercise and being physically active will help you live longer. Regular stretching or yoga is helpful in keeping joints and ligaments supple. If you are sedentary, even a small increase in activity can enhance your longevity by a couple of years. People who engage in plenty of light movement have a lower risk of developing a disability and losing their capacity to care for themselves. People who want to increase longevity may do so by running or engaging in regular activity. In one study done at Stanford University in California, middle-aged members of a runner's club were half as likely to die over a 20-year period as people who did not run. Running reduced the risk not only of heart disease, but of cancer and neurological diseases such as Alzheimer's. Any type of exercise will likely do the trick. Fitness, strength and flexibility do not inevitably fade away with age, and are more often a matter of lifestyle choicest. Often, the discomforts of middle-age, like lower back pain or stiff joints, are blamed on aging alone. However, a well-rounded exercise routine that includes aerobic activity, strength training and stretching can help people offset the effects of aging. Avoid extreme physical activities. Marathon runners have increased stiffness of the large arteries, suggesting that some types of regular high-intensity exercise may actually be bad for the heart, potentially leading to hardening of the arteries, high blood pressure, heart attack and even death. A moderate running regimen -- for instance two to three hours per week appears best for longevity. People who get either no exercise or high-mileage runners both tend to have shorter lifespans than moderate runners. The study was conducted by the Cardiovascular Research Institute at the Lehigh Valley Health Network in Allentown, PA and published in April 2014. Everyone knows that walking limbers the aging body, but did you know it keeps the mind supple as well? Walking can actually boost the connectivity within brain circuits, which tends to diminish as the grey hairs multiply. Frontiers in Aging Neuroscience, Published 2010. Excess TV viewing, such as more than 2 hours a day, shortens lifespan. Almost any amount and type of physical activity may slow aging deep in our cells, and middle age is a critical time to get the process rolling.

Even small changes can help confirmed couch potatoes improve their health and enhance longevity. Although the benefits of exercise and a healthy diet are well known, people may think they have to make major changes in their lifestyle to obtain any results. But any increase in physical activity is beneficial.

Basic lifestyle habits lead to a longer lifespan. Exercise, a healthy diet and good sleep slow down the aging process at a cellular level, and protect the body and mind against the harm caused by stress. July 29, 2014, Molecular Psychiatry

5. Avoid smoking cigarettes. Smokers die ten years younger on average than non-smokers As if smokers need another reason to kick the habit, California scientists have discovered that nornicotine, a byproduct of nicotine, the substance that makes cigarettes so addictive, causes a type of chemical reaction in the body similar to that which occurs when sugar is scorched or food goes bad. This reaction is thought to play a role in diabetes, cancer and other diseases. The interaction between sugars and proteins can produce substances called advanced glycation endproducts, or AGEs. The accumulation of AGEs appears to contribute to the aging process and certain diseases. Guided imagery may help quit smoking. 6. Loving connectoinsHave strong connections to others, whether through family and relatives, marriage, children, pets, or connecting with nature, planet earth, and the universe. Have loving and caring friends. Research suggests that having a strong network of friends helps people live longer.

7. Get a deep sleep. Getting a deep sleep is probably the most important longevity secret.

8. Keep your mind young and active by learning. Doing crossword puzzles or watching the show Jeopardy can do wonders in maintaining mental sharpness and word recall. The more educated you are, the less likely you are to become chronically ill or disabled, and your chances for greater longevity will improve. But, the amount of money you make plays a bigger role in whether your illness progresses.

9. Try to surround yourself with nature. Green trees in the neighborhood, sunshine in the home, are linked to longevity.

10. Tooth care Take care of your teeth and mouth to prevent or minimize gum disease and dental caries. Use a soft brush after a meal and then floss. Smoking can cause gum disease.

Addition longevity tips Work as long as you can. It is widely held that early retirement is associated with longer life expectancy and later retirement is associated with early death. Survival rates appear to improve with increasing age at retirement. This seems to be the case for both high- and low-income groups.

Participating in volunteer activities may add years to an older person's life. Volunteering may improve health by expanding retirees' social networks, increasing their access to resources and improving their sense of self-worth.

Drink more tea, and less sodas and sugared drinks. Limit fruit juice intake to no more than 8 ounces a day since fruit juices have a lot of fructose. Many delicious herbal teas are available, including green tea, ginger, rooibos herb, rose hips, mint, fennel herb, licorice, etc.

10. Limit coffee intake to one or two cups - chronic coffee consumption has a detrimental effect on aortic stiffness and wave reflections, which may increase the risk of cardiovascular or heart disease.

Drink an ounce or two of wine a few times a week.

Do DHEA hormone and pregnenolone hormone increase longevity? In high doses, DHEA and pregnenolone may increase the risk for cancer and heart arrhythmia. But it is possible, that in some people, low doses such as 1 or 2 mg may have health benefits.

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Additional longevity enhancers: Being financially stable Having a satisfying career Healing old and new emotional wounds Having a personal religious or philosophical belief system that gives meaning to this world. Driving safely, wearing seat belts, minimizing the use of cell phones while driving.

Genetics One of the most important influences on longevity is genetics, something we cannot influence with our present scientific knowledge. People who have parents and grandparents who live long are more likely to also live a long life.

High blood pressure and longevity Hypertension can take years off both life expectancy and time lived free of disease. Research, based on data from a long-running U.S. heart-health study, found that the impact of high blood pressure on life expectancy may be more significant than previously estimated. Researchers found that high blood pressure at the age of 50 shaved about 5 years off men's and women's lives. It also caused them to endure 7 more years with cardiovascular disease compared with their peers who had normal blood pressure in middle-age. It's well known that high blood pressure raises the risk of heart disease, stroke and kidney failure, but only a few studies have looked at how blood pressure affects longevity.

Stress reduction Chronic psychological stress is associated with accelerated shortening of the caps, called telomeres, on the ends of chromosomes in white blood cells -- and thus hasten their demise -- according to a report in the Proceedings of the National Academy of Sciences. Telomeres promote chromosome stability. Telomeres shorten with each replication of the cell, and cells cease dividing when telomeres shorten sufficiently. The team investigated the theory that psychological stress affects telomere shortening and thereby contributes to a decrease in longevity. Their study included 39 healthy, premenopausal women who were primary caregivers for a child with a chronic illness, and 19 age-matched mothers of healthy children who served as a comparison "control" group. Stress was measured with a standardized questionnaire, and telomere length was measured in participants' blood samples. Within the caregiving group, the longer that a woman had been a caregiver, the shorter was the length of telomeres. In the 14 women with the highest stress scores, telomeres averaged 3,110 units in length; the 14 with the lowest stress had telomeres that averaged 3,660 units. In adults, telomeres shorten by an average of 31 to 63 units per year, so the scientists estimate that the 550-unit shortening in the high-stress group translates to 9 to 17 additional years of aging.

Mitochondria and acetyl-l-carnitine Decline in mitochondrial function may lead to cellular energy deficits, especially in times of greater energy demand, and compromise vital ATP-dependent cellular operations, including detoxification, repair systems, DNA replication, and osmotic balance. Mitochondrial decay may also lead to enhanced oxidant production and thus render the cell more prone to oxidative insult. In particular, the heart may be especially susceptible to mitochondrial dysfunction due to myocardial dependency on beta-oxidation of fatty acids for energy and the postmitotic nature of cardiac myocytes, which would allow for greater accumulation of mitochondrial mutations and deletions. Thus, maintenance of mitochondrial function may be important to maintain overall myocardial function. Herein, we review the major age-related changes that occur to mitochondria in the aging heart and the evidence that two such supplements, acetyl-l-carnitine (ALCAR) and (R)-alpha-lipoic acid, may improve myocardial bioenergetics and lower the increased oxidative stress associated with aging. We and others have shown that feeding old rats ALCAR reverses the age-related decline in carnitine levels and improves mitochondrial beta-oxidation in a number of tissues studied. However, ALCAR supplementation does not appear to reverse the age-related decline in cardiac antioxidant status and thus may not substantially alter indices of oxidative stress. Lipoic acid, a potent thiol antioxidant and mitochondrial metabolite, appears to increase low molecular weight antioxidant status and thereby decreases age-associated oxidative insult.

Japanese women had a life expectancy of 85.59 years in 2004, making them the world's longest living group for the 20th consecutive year. Japanese men trailed with a life expectancy of 78.64 years, which placed them second for longevity after Icelandic men, who live an average of 78.8 years.

Octogenerian has a baby An 88-year-old Indian farmer has become the father of a baby boy. He says he has sex daily and wants more kids. "I don't want to live to 100 but, as long as I live, I should be able to enjoy sex," said Virmaram Jat, who lives in a village in the Barmer district in the western desert sate of Rajasthan. The prosperous farmer, with a flowing white beard and a weather-beaten face, says he takes long walks every day and has been drinking fresh camel milk since childhood. The paper reported his latest wife -- his third -- is 45 years younger and delivered male twins last month, but only one boy survived. The octogenarian is a vegetarian and has never smoked cigarettes or drunk alcohol.

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Thursday, August 4th, 2016

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