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Its no secret that Texans like tequila. In fact, its a point of pride. Between patio margaritas, rooftop palomas and late-night shots, we consumed a little more than 18 million liters of the agave-based spirit in 2018. That accounts for a respectable one-ninth of the entire countrys consumption, according to data from IWSR Drinks Market Analysis.

Of course, like all things delicious and from the earth, sustainable agricultural practices are key to ensuring that its still around for us to enjoy long term.

The future of agave depends upon genetic diversity, says Grover Sanschagrin, the Jalisco, Mexico-based co-founder of tastetequila.com and the Tequila Matchmaker app. Right now, the entire industry is using blue agave with the exact same genetic code, because they are harvesting the hijuelos, baby plants that are clones of the mother.

The clones are an efficient means to an end. If allowed to flower and sexually reproduce on their own a process that often takes as long as 12 years agave plants wont have enough juice left to distill. To combat this dilemma, growers clone the agaves, ensuring theyre able to harvest the plants when perfectly ripe, usually between six and eight years of age. But, while efficient, the practice is inherently risky. If one gets a disease, it could wipe out all of the plants, Sanschagrin says.

Its a risk that some tequila producers are hoping to mitigate. And the steps they choose to take now will affect tequilas availability and quality in the future.

One brand at the forefront of progressive sustainability practices is El Tesoro, which is made at the La Altea Distillery located in the Jalisco highlands, about 6,000 feet above sea level. Led by master distiller Carlos Camarena, El Tesoro does things the old way the hard way. Agaves are grown entirely on the familys estate, hand-harvested after seven to eight years, slow-cooked in brick ovens and then crushed with a 2-ton stone called a tahona.

But even a brand steeped in tradition knows that it must look toward the future to ensure its success. Thats why Camarena is part of the Bat Friendly Tequila and Mezcal Project, which promotes biodiversity among agave plants. Today, El Tesoro allows between 2% and 5% of its plants to reach full maturity and bloom. For tequila producers, setting aside even a small percentage of the crop represents a substantial financial hit, as those plants cant be harvested, distilled and monetized.

Its good news for the bats, though. They are natural pollinators of agave plants, feeding on the nectar of mature plants and cross-pollinating from field to field. Its a symbiotic relationship. Formerly endangered species like the lesser long-nosed bat have more food to eat now, and their pollinating efforts promote biodiversity among the agaves.

Its too soon to know exactly how successful the project will be in the long run. Many scientists believed that, after so many years of cloning, it would be impossible for the blue agaves to reproduce sexually. But the results have already defied expectations. Camarenas team has been nurturing seedlings in a greenhouse, and roughly 5% have yielded sprouts, potentially representing a new genetic wave of agaves.

Camarena is playing the long game. Maybe well see results in 80 or 100 years, he says, but this isnt something were doing for our own lifetime.

While El Tesoro is one of the innovators leading the sustainability charge, its not alone. Ubiquitous giant Patrn commissioned a study at the National Center of Genetic Resources, Mexicos biodiversity bank in Jalisco, to analyze blue agaves genetics in hopes of establishing future recommendations for the industry that will promote long-term sustainability. And even smaller producers such as Ghost are playing a part.

People in the industry tend to look at agave sustainability as an issue that should be addressed by the large tequila companies, says Chris Moran, founder and CEO of Ghost Tequila. I dont agree at all. This is a matter of importance that every tequila producer needs to take seriously, to share in the responsibility to ensure the longevity of this crop.

He notes that they control their own agave fields, which allows them to institute responsible agronomy practices, such as planting alternate crops after agave harvests to allow the soil to regenerate.

But its not just the distillers who have a say in the matter. Bars, restaurants and retail shops can make an impact via the products they choose to carry.

According to Chris Dempsey, a bartender at Atwater Alley and the mezcal- and tequila-focused La Viuda Negra, its important for bars to consider how spirits are made when deciding what to stock and pour. He notes that his bars wont carry any products made with a diffuser, a machine that significantly shortens the harvest-to-bottle timeline and strips out a lot of the agaves character. He prefers to support the people who put in the time and effort to produce the best possible products, noting a few favorite brands, including Siembra Valles, Tequila Ocho and El Tesoro.

Camarena has been instrumental in sustainability and biodiversity, Dempsey says. He is the leader to watch when talking about and practicing sustainability with agave and Mexican spirits.

Spirits right now have the ability more than ever to be responsible, not just in production, but socially, says Jose Gonzalez, a bartender at Midnight Rambler inside the Joule hotel. It says a lot for a company when they put their money and their plants on the line.

He adds that Camarena is a guardian of agave plants, not just an owner, and that mindset impacts everything from the distillerys light environmental footprint to the quality of the product.

People should care about what they put in their bodies as well as who it affects, like the producers and farmers, Gonzalez says. As much as we go to the farmers market to grab local produce, we should know who grows the agave.

Dempsey also urges consumers to fight the good fight.

Think about it, he says. You want to work out and eat all this amazing organic food, but then you go and drink some subpar spirits just because of marketing and a low price. That defeats the purpose of being healthy. If you really want to help the cause, dont drink diffuser tequila, and help support any sustainable agave program.

According to Sanschagrin, at todays market prices, each 1-liter bottle of traditionally-made 100% agave tequila contains about $10.70 worth of agave inside. So, while we consumers dont have a hands-on impact on the plants growing in Mexico, we can exert our influence with how we choose to spend our hard-earned tequila money.

Read the rest here:
The future of tequila: How clones, bats and biodiversity will help agave survive - The Dallas Morning News

It's been 17 years since Cleveland Clinic hosted its first Medical Innovation Summit. As the 2019 version of conference officially launches Monday morning, its organizers say this year's gathering reflects the changing landscape of healthcare innovationnot only in terms of topics, such as sessions exploring AI, augmented reality, and virtual realitybut also in terms of who's standing at the dais and who's attending.

Through Wednesday, entrepreneurs from startup companies, investors, and payers will join the venerated researchers and practitioners who once were the primary focus of the Summit. Also present: key players from companies outside the traditional healthcare sector, including Amazon Web Services, CVS, Google, and Microsoft.

"While the technology is interesting, the bigger story is the die is not cast in terms of who will disrupt healthcare," saysWilliam Morris, MD, executive medical director, Cleveland Clinic Innovations. "Healthcare disruption will come from all angles. That's the power of this Innovation Summit."

For example, late Monday Eric Lefkofsky, co-founder and chairman of Groupon will present a keynote address. Four years ago, after Lefkofsky's wife was diagnosed with cancer, he founded Tempus to leverage data analytics, genomics, and artificial intelligence to provide precision medicine to patients.

"Health issues touch all of us," says Morris, adding that today people and companies outside of traditional spheres of influence have been empowered to innovate and take action. "It's an interesting theme because it challenges the status quo."

On Tuesday, Morris says, Craig Mundie, senior advisor to the CEO of Microsoft, who is former chief research and strategy officer for the company, will discuss the role of technology in transforming the healthcare delivery industry.

"Again, it's very personal story, talking about the promises of new technologies and how they can actually benefit all patients," says Morris. "I think there's an interesting thread for an audience member to ask, 'Who are these people? How are they navigating this?' It's so diverse. A tremendous takeaway is that it is incumbent on us all to reimagine healthcare."

In the past the Summit focused on specific disease states and medical devices, says Susan Bernat, general manager of strategic marketing, Cleveland Clinic Innovations.

"We realized that we were truly missing something as healthcare is evolving," Bernat says. Cleveland Clinic treats each of its patients as a whole person, not just a disease, she says. The conference needed to reflect that dynamic, which led to this year's theme, "Caring for Every Life Through Innovation."

"Now it's a more well-rounded conversation," Bernat says.

Morris says that those involved in healthcare innovation bring optimism to the U.S. healthcare industry.

"There's an esprit de corps in our DNA that we will solve [the challenges]," he says. "I don't think there'll be one simple eureka moment. It's going to be a lot of work, a lot of collaboration. But the great news is, there is such passion to do better. The focus has moved beyond innovating for the sake of innovating and to challenge traditional status quo of how healthcare is being rendered."

Some highlights from Summit include:

The 2019 Cleveland Clinic Medical Innovation Summit takes place October 2123 at the Huntington Convention Center of Cleveland in downtown Cleveland. The Summit is organized by Cleveland Clinic Innovations, the business development and commercialization arm of Cleveland Clinic.

Mandy Roth is the innovations editor at HealthLeaders.

Go here to read the rest:
Outsiders Are In: The Cleveland Clinic Innovation Summit Evolves - HealthLeaders Media

Over the past few months Bernie Sanders has often remarked that hes in great shape. I am blessed to have been in good health my entire life, he told the Washington Post earlier this year. I honestly cant remember the last time I missed work because of illness. I bought it: The guy seemed reasonably fit and sharp. Then, last week, he suffered a heart attack.

Given his age, its not all that surprisingabout a fifth of men in their 60s and 70s have heart disease; by age 80, nearly a third do. On Inauguration Day, he will be 79, which makes him 40 years older than the oldest of millennials, his most devoted demo. That also makes him the oldest serious contender, but many of his opponents arent spring chickens, either: Joe Biden will be 78, Donald Trump 74, and Elizabeth Warren 71.

This grayest-ever crop of frontrunner candidates has made some people wonder whether there should be a legal age limit on running for president. Indeed, other fields turn aging employees out to pasturecommercial airline pilots, employees of the United Nations, and judges in many states arent allowed to practice into their 70s. So isnt it conceivable that the presidency of the United Statesby many measures literally the hardest job in the worldshouldnt go to someone prone to senior moments? And if we have a lower age limit, why not an upper one?

Consider that Jimmy Carter, the oldest living president at 95, said recently, If I were just 80 years old, if I was 15 years younger, I dont believe I could undertake the duties that I experienced when I was president.

I recently called up some other accomplished older people to see what they thought about an aging president. Their responses were not exactly encouraging.

A 96-year-old museum docent barked, I have absolutely no interest in talking to you about that, and hung up.

The oldest mayor in the United Stateswho is 80 and runs the city of Stafford, Texastold me in an email that he would be happy to visit by phone but then never got around to calling me back.

An 87-year-old retired CEO said, Hold on, let me get out of my wheelchair. No, Im just kidding. Are you young and pretty? Will you go out with me? No, Im just kidding.

After that initial round of interviews, you can guess I wasnt exactly bullish about the idea of a president pushing 80. So I decided to check in with the experts: scientists who study how the aging process affects our bodies and minds. They painted a very different picture.

Nir Barzilai, an endocrinologist with Albert Einstein College of Medicine, studies the genes of a group of long-lived Ashkenazi Jews. Barzilaiwho is prone to comments like Age means nothing to me! and I know someone who just went to Machu Picchu for her 100th birthday!has been able to show that about 60 percent of the 100-year-old women hes studied have certain unusual mutations in their growth genes. We have discovered longevity genes, he said. Unfortunately, he then added, Do the candidates have them? I have no idea.

Short of sharing a full genetic sequencing, Barzilai says that family history is a pretty good predictive factor. That bodes well for Trump, Warren, and Biden, whose parents all lived well into their 80s. But then what to make of Sanders, who has already outlived both of his parents by several decades (and is expected to make a full recovery from his heart attack)?Barzilai acknowledges its not just about genes; social and environmental circumstances also help determine how long and how well a person lives.

I found out that more powerful predictors of both longevity and cognitive stabilitymore powerful than even geneticsare three external factors: education, race, and wealth. Countless studies have found a correlation between income level and lifespan; a 2016 study published in the Journal of the American Medical Association, for example, found that on average, the richest 1 percent of American men live 14.6 years longer than the poorest 1 percent; for women the difference is 10.1 years. Thats not surprising: Being wealthy means you have access to good health care and good control over your diet and exercise.

Relatedly, education level matters, tooand even more so along racial lines. In 2012, University of Illinois at Chicago gerontologist and public health researcher Stuart Jay Olshansky sorted deaths in the United States by age, race, and number of years of schooling. He found that on average, black men who hadnt finished high school lived 14.2 years less than white men who had completed 16 or more years of education; for women that figure was 10.3 years. (Its important to note that these racial differences probably have to do with lack of opportunity for African Americans, not any biological difference.)

Education also seems to have a strong protective effect against dementia: A 2018 University of Southern California study found that most people who have graduated from college can expect to prevent cognitive decline into their 80s, while people with a high school education often begin to experience it in their 70s. Its not that education actually prevents the changes in the brain associated with dementia, explained Joe Verghese, another Albert Einstein gerontologist. Rather, education seems to help people compensate for those changes. The theory is that people who are highly educated and intellectually engaged will be able to stave off the effects of this disease, he said.

When you consider these external factors, good genes dont seem as important. All of the presidential candidates are wealthy; all are exceptionally well educated. Take Sanders: Its valid to speculate that perhaps one reason he has lived so much longer than his parents is that he has a college degree and robust finances, while his parents were poor immigrants who worked all their lives.

University of Illinois Olshansky used actuarial tables to calculate the lifespan and healthspan of each candidatebasically, the risk that theyll die or become cognitively or physically disabled while in office. Taking into account wealth and education level he found that all the contenders stand at least a 76.8 percent chance of surviving their first term, most of them higher. (For most, the odds of living through a second term are also high, though for Sanders and Biden, they drop to 66 percent and 70 percent respectively.)

So its likely that by dint of privilege and circumstance, even the oldest contenders stand a pretty good chance of surviving the presidency. Fair enough. But that still left me wondering about their mental health and general with-it-ness. Would they, too, last?

The geriatric psychologists I talked to all assured me that contrary to popular belief, elderly people are no more prone to depression, anxiety, and other psychiatric disorders than their younger counterparts. Ellen Langer, a Harvard University psychologist who specializes in geriatric patients, railed against the stereotype of the socially weird old person. Its not that their age-addled brains make them behave strangely; rather theyve mastered the fine art of not caring. At 30 you might be mortified that you have spaghetti sauce on your shirt and you have to go a meeting, says Langer. At 70, you might say, Please excuse this, as you can see I was excited about the spaghetti I was eating!

In short, Langer says, life experience leads to perspective. And if you have those qualities, so what if you still think people listen to records? What are millennial staffers for, if not to show the president how to, say, use an iPad for briefing updates? (Speaking of millennials, maybe its time we rethink the requirement that a president must be at least 35, which hasnt changed since Continental Congress delegate Tench Coxe wrote that the president cannot be an idiot, probably not a knave or a tyrant, for those whom nature makes so, discover it before the age of thirty-five, until which period he cannot be elected. Today, you could probably figure all that out from a 25-year-old candidates Twitter feed. And we know people can act tyrannical across ages.)

In any case, the gerontologists told me that age wouldnt play a major role in their decision on Election Day. And their research suggests that setting a legal age limit for president probably doesnt make sensethough that may end up being irrelevant: The way things are looking now, Americans wont have much of a choice but to vote for someone who was born before there were zip codes or magic markers or antihistamines. Thats too bad, since there are signs that Americans are clamoring for younger, more diverse political leadershipsee, for example, the upwelling of enthusiasm for Alexandria Ocasio-Cortez and her squadmates. And last year, when I was talking to voters about the 44-year-old African American Georgia gubernatorial candidate Stacey Abrams, I heard over and over from people who were thrilled to see a candidate that finally looked like them.

In this country, the same set of extreme social privileges that propel someone to the position of frontrunner presidential candidate also protect against the typical ravages of old age. And that single fact, for better or worse, is a stronger predictor of candidates health than any senior-moment gaffe they might have over the coming months. Its entirely possible, Olshansky told me, that some of these folks running for president are super-agers. We should all be so lucky.

Image credit, from left:Bill Clark/Getty; Mario Tama/Getty; Chip Somodevilla/Getty; Joe Raedle/Getty

Read more:
It's No Coincidence That the Top Presidential Candidates Are All So Old - Mother Jones

In his all-conquering career, its the final, elusive frontieran impossible dream that Eliud Kipchoge will now try to make a reality.

The 34-year-old has done it allOlympic gold, world title, the marathon world recordbut there is one thing he has yet to tick off his bucket list: a sub-two-hour marathon.

Many ideologies [have] been going that no human will break the two-hour mark but personally, I have dared to try, Kipchoge said in a video of the INEOS 1:59 Challenge documentary series. I am doing it to make history.

He is, without question, the greatest marathoner of all time, but in a park in Vienna, Austria, on Saturday, Kipchoge will aim for immortality. The start time for the event will be 8:15 a.m. in Vienna; 2:15 a.m. ET.

Fans know that he has come close before. In May 2017, the Kenyan clocked 2:00:25 on a formula one racetrack in Monza, Italy, during Nikes Breaking2 project. It was the fastest marathon ever run, but did not count as an official world record because of the use of rotating pacemakers.

Kipchoge went on to set the official world record at last years Berlin Marathon, running 2:01:39 to carve 78 seconds off the previous mark. Shortly after winning his 10th straight major marathon in London this past April, he announced his next project: the INEOS 1:59 Challenge.

In his bid to push back the boundaries of human ability, he thinks hell have more than luck on his side. I have a rich experience from Monza, he said. I am confident I will beat the mark.

Many of the people close to Kipchoge are as confident as he is. His manager, Valentijn Trouw, has overseen his preparation. In an interview with Runners World on Wednesday, he said Kipchoge is primed for the task.

If we look at the whole training circle and compare it with preparations for London (in 2019) or Berlin (in 2018), he is in a nice position, Trouw said.

I am confident I will beat the mark.

Trouw paid several visits to Kipchoge as he trained for the attempt in Kaptagat, Kenya, and having been there for every step of Nikes Breaking2 project, he sees a difference in Kipchoges mindset this time.

Two years ago he was training his mind for seven months to convince himself he could do it. The moment we talked about this, Eliud had that internal feeling: If I train well and it all comes together on the day, Im going to do it.

No stone has been left unturned in preparation. With the financial backing of INEOS, a petrochemical company owned by the richest man in Britain, Jim Ratcliffe, every detail has been orchestrated to maximize Kipchoges chances.

The coursethe Prater park in Viennawas picked after a worldwide search using software to find locations that have ideal parameters in temperature, humidity, air pressure, wind speed, elevation, and precipitation at this time of year.

The race is scheduled to begin early on Saturday on the citys Reichsbrcke Bridge, and Kipchoge will then make a 1.2K run to the Praterstern roundabout, where the road has been resurfaced with a camber to maximize Kipchoges efficiency as he circles it.

The initial run to the park features an elevation drop of 16 meters and once there, Kipchoge will complete four laps of a 9.6K circuitand a final stretch to complete the full distancethat is almost completely flat, with just 2.4 meters of elevation change. After the four circuits,

Forty-one world-class distance runners have been recruited as pacemakers, and they will take turns in a different formation to that seen in the previous attempt. Five athletes will run in front of Kipchoge in a V-shape, with two athletes just behind him to either side, which was found during testing as the most efficient way to reduce drag. Officials from INEOS noted that Kipchoge and all the pacers are being tested both in and out of competition by the Athletics Integrity Unit (AIU), which is the same testing unit used by the World Marathon Majors.

The time Kipchoge runs will again not count as an official world record because of the use of rotating pacemakers and because he will be handed drinks from a bicycle rather than from a table, as required by the sports governing body (IAAF) for record-eligible races.

However, all other IAAF guidelines will be followed to ensure the achievement, if it happens, maintains a sense of credibility.

While Nikes attempt was not open to the public and took place on a near-deserted racetrack, this event is supposed to be the opposite, with organizers hoping close to 20,000 will line the roads in The Prater to lend their support.

Having a crowd is absolutely crucial, giving him that encouragement, bringing that energy, said Fran Millar, CEO of Team INEOS, in one of the documentary videos leading up to the event. Its going to be a huge boost for Eliud.

A car will once again be driven in front of the runners at a controlled pace of 2:50 per kilometer (4:33 per mile), with a line projected on the road for runners to follow.

During the race Kipchoge will consume a carbohydrate drink made by Maurten, a Swedish manufacturer, and every time he takes a drink from a bottle and discards it, it will be picked up and weighed to measure exactly how much was consumed, with feedback given to guide future intake.

The biggest performance gain, however, may come from Kipchoges shoes. Its a controversial topic in running given the slew of records that have fallen since Nike introduced its Vaporfly 4% during its Breaking2 attempt in 2017. The shoe features a carbon fiber plate to help propel athletes forward, and in April this year Kipchoge wore its latest version, the ZoomX Vaporfly Next%, which was 15 grams lighter and featured a thicker midsole.

In recent months, Kipchoge has been training with a new version of the shoe, which is set for release next year. It will be mainly a follow-on from the shoe he was using in Berlin and London, Trouw said. He has done quite a lot of training sessions in the shoe to get familiar.

At the time of publication Nike had not responded to questions about the shoes specifics, but an industry insider has told Runners World it is substantially more efficient than both previous editions.

Of course, the most important ingredient of all will be Kipchoges fitness. After the London Marathon in April he ran easy for four days and then took three weeks completely off running. For the next month he ran three to four times a week and hit the gym for two and a half hours on the other days, doing weight training, step aerobics and flexibility work.

That laid the foundation for what came next, with Kipchoge then following his usual four-month marathon buildup under the guidance of Patrick Sang, the coach and mentor who has steered his career for the past two decades.

Courtesy of INEOS 1:59 Challenge

Kipchoge typically ran a fartlek on Tuesdays, a long run on Thursdays and a hard session of intervals on Saturdays, with the rest of his week filled with easy to steady running.

A test event was organized in Vienna in late August, and while the plan was initially for Kipchoge to attend and familiarize himself with the course, he decided it was better to stay in Kenya and avoid the interruption to his training.

As a result he got his first look at the course on Tuesday after arriving in Vienna, where the 41 pacers have been practicing their formations all week. One of those is U.S. 1500-meter athlete Matthew Centrowitz, who spoke in glowing terms about Kipchoge at this years world championships.

Hes got the most unbelievable range of any athlete ever, Centrowitz said. We could all learn a little something from him about his longevity, the enjoyment he looks like he has even when hes struggling out there. If [he makes] history, thats something I want to be a part of.

Fellow Olympian Lopez Lomong was part of the pacing team during Nikes Breaking2 attempt, and the U.S. distance star is equally impressed by Kipchoge. Hes a very calm guy, dialed in, Lomong said. Theres a lot of things I like to emulate from him, how humble he is. He doesnt do it for himself, he does it for the community, to open the eyes of athletes that if he can do it, then we can do it as well.

Lomong is certain Kipchoge will achieve his goal, predicting a finishing time of 1:59:36, while Centrowitz is also confident, predicting 1:59:52.

As with all great sporting barriers, much of the challenge is mental. In that department, few can rival Kipchoge.

From my experience over many years he can block pain, put it at the back of his mind until the race is done, Kipchoges long-time physiotherapist Peter Nduhiu said in a documentary video showing his training. Its something that is so unique to him.

Kipchoges mental strength is something he takes seriously. He devours self-help books for ways to find a psychological edge.

Some people think its genetics, that you either have a strong mind or you dont, but its something you can train and improve, Trouw said. This is where day in, day out, Eliud gets stronger and stronger.

Trouw has been with Kipchoge in Vienna since Tuesday, and while he is cautious not to make any bold predictions, he sees in his star athlete as having a calm, cool confidence that bodes well as he prepares to go up against the ultimate barrier.

Eliuds mindset at the moment is really strong, Trouw said. He absolutely believes he is going to do this.

See the rest here:
What Will It Take for Eliud Kipchoge to Break 2-Hours? - runnersworld.com

DUBLIN, Oct. 10, 2019 /PRNewswire/ -- The "Global DNA Read, Write and Edit Market" report has been added to ResearchAndMarkets.com's offering.

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The scope of the report includes DNA read, write and edit technologies, applications, industries, initiatives, patents, and companies. The markets for read, write and edit products and services are given for 2017, 2018, 2019 (estimated) and 2024 (forecast).

This report reviews the main read, write and edit technologies and explains why genetic variation is important in clinical testing and disease. It then discusses significant large-scale research initiatives that impact read, write and edit applications. Of particular interest is a discussion of population-scale sequencing projects throughout the world, and their likely impact. The main market driving forces for read, write and edit products and services are listed and discussed.

The report quantifies each of the main market segments. The read (sequencing) market is quantified by delivered format, including sequencing workflow products (sample preparation kits and reagents, sequencing instruments and consumables, and informatics) and sequencing services (clinical diagnostics and sequencing services to applied market customers).

The sequencing workflow products market is quantified by type, that is, DNA isolation and extraction; target enrichment; library preparation; and informatics/ecosystems. The sequencing instruments and consumables market is given by platform (Sanger, NGS, and 3GS).

The sequencing services market is analyzed by end-user application (applied, clinical, and R&D). Within sequencing services, the applied market is analyzed by end-user application (agriculture, biopharma, consumer, microbiology, population-scale genomics, synthetic biology and other).

Also within sequencing services, the clinical market is analyzed and quantified by disease category (cardiovascular, clinical microbiology and infectious diseases, Mendelian disorders, metabolic/immune disorders, neurology, oncology, reproductive health, and transplant medicine).

The DNA write (synthesis) market is quantified by product type (oligonucleotides, synthetic biology parts, genes, and RNA therapeutics). The oligonucleotide market is analyzed by application (gene editing, sequencing, PCR, FISH, microarray, gene synthesis and other). The gene market is quantified by gene type (standardized, value-added). Finally, the RNA therapeutics market is quantified by platform (RNA interference, antisense oligos, micro RNA modulation, and mRNA) and by disease category (cancer, hematology, musculoskeletal, neurology, and rare diseases).

The DNA edit (gene editing) market is quantified by application (agriculture, biopharma, diagnostics, and therapeutics); editing platform (CRISPR, meganuclease, TALEN, ZFN). The gene-editing agriculture market is analyzed by product type (crop/seeds, livestock). The gene-editing biotechnology market is analyzed by product type (kits and reagents, cell line engineering, animal models and services). The gene-editing therapeutics market is analyzed by disease category (eye and rare diseases).

Specific geographic markets discussed include North America, Europe, Asia-Pacific, and the rest of the world (ROW).

Industry sectors analyzed include next-generation sequencing; long-read sequencing; DNA synthesis; RNA therapies; and gene editing.

More than 320 companies in the read, write and edit industry are profiled in this report.

The author also provides a summary of more than 180 of the main industry acquisitions and strategic alliances that took place from January 2018 through June 2019, including key alliance trends.

Story continues

Market Summary

The DNA read, write and edit industry is at the beginning stages of its growth story; penetration of the key markets is still at an early stage. The data indicates that there is a significant future upside for sequencing across research, metagenomics, agriculture, synthetic biology, and clinical applications, among others.

The situation is similar for DNA writing and editing technologies, with clinical therapeutic applications, in particular, providing an enormous total available future market that is yet to be significantly penetrated. Major successes in this industry include the adoption of next-generation sequencing (NGS) for noninvasive prenatal testing; enabling the roles of synthetic DNA oligonucleotides and genes in the rise of the synthetic biology industry; and rapid adoption of CRISPR gene editing by research institutions and biopharma industries.

There is increasing interplay among the three DNA technology platforms, giving rise to innovative corporate strategies. For example, Arbor Biotechnologies employs sequencing, gene synthesis, and artificial intelligence to perform high-throughput discovery of biomolecules, including new CRISPR proteins.

Report Scope

Key Topics Covered

Chapter 1 Introduction

Chapter 2 Summary and Highlights

Chapter 3 Overview

Chapter 4 Technology Background

Chapter 5 DNA Read, Write and Edit Initiatives

Chapter 6 DNA Read, Write and Edit Applications

Chapter 7 DNA Read, Write and Edit Industries

Chapter 8 Acquisitions and Strategic Alliances

Chapter 9 DNA Read, Write and Edit Markets

Chapter 10 Patents

Chapter 11 Nucleic Acid Read, Write and Edit Company Profiles

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/7jlxd8

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

Media Contact:

Research and Markets Laura Wood, Senior Manager press@researchandmarkets.com

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Analysis on the Global DNA Read, Write & Edit Market, 2017-2019 and Forecast to 2024 - Yahoo Finance

For the most comprehensive take on all of David Sinclairs recommendations and the best ideas on optimizing healthspan, check out The Table of Longevity | The 5 Pillars to Optimize for Increasing Healthspan and Living Your Best LifeKey Takeaways

NAD+ is responsible for hundreds of critical biological processes, including creating energy, regulating sleep/wake cycles, and maintaining healthy DNA. Heres the problem: NAD+ declines with age no matter how much you exercise and how well you eat. So what can you do? You have a few options, but the most promising is supplementing with the oral NAD+ precursor, NR (nicotinamide riboside). For us at Podcast Notes, hands down, when it comes to a brand of NR, we cant recommend Elysium Basis enough (use the code podcast45 at checkout to receive $45 off a semi/annual subscription). We, Matt and Yoni, have been researching the company and trying Basis out for the past 3 months. Basis is a proprietary formulation of crystalline NR and pterostilbene that supports cellular health by increasing and sustaining NAD+. Long-term health starts at the cellular level. If you want to improve your healthspan and increase your energy, replenish your NAD+ levels in the most efficient way possible with Elysium Basis.

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David Sinclair, Ph.D. - The Joe Rogan Experience #1349 ...

All cells have a programmed lifespan by which they are synthesized, multiply, and eventually undergo apoptosis (cell death) when they are no longer functional.

It often helps to think of cellular replication as old-fashioned photocopy machine: the more a cell copies itself, the more blurry and misaligned the image becomes. Over time, the genetic material of the cell (DNA) begins to fracture and the cell itself becomes a pale copy of the original. When this happens, programmed cell death allows a new cell to take over and keep the systems running.

The number of times a cell can divide is bounded by a phenomenon known as the Hayflick limit. This describes the action by which the process of division (known as mitosis) progressively degrades the genetic material, specifically the part of DNA called a telomere.

The Hayflick limit dictates that the average cell will divide between 50 to 70 times before apoptosis.

Chromosomes are thread-like structures located inside the nucleus of a cell. Each chromosome is made of protein and a single molecule of DNA.

At each end of a chromosome is a telomere which people will often compare to the plastic tips at the ends of a shoelace. Telomeres are important because they prevent chromosomes from unraveling, sticking to each other, or fusing into a ring.

Each time a cell divides, the double-stranded DNA separates in order for the genetic information to be copied. When this happens, the DNA coding is duplicated but not the telomere. When the copy is complete and mitosis begins, the place where the cell is snipped apart is at the telomere.

As such, with each cell generation, the telomere gets shorter and shorter until it can no longer maintain the integrity of the chromosome. It is then that apoptosis occurs.

Scientists can use the length of a telomere to determine the age of a cell and how many more replications it has left. As cellular division slows, it undergoes a progressive deterioration known as senescence, which we commonly refer to as aging. Cellular senescence explains why our organs and tissues begin to change as we grow older. In the end, all of our cells are "mortal" and subject to senescence.

All, that is, but one. Cancers cells are the one cell type that can truly be considered "immortal." Unlike normal cells, cancer cells do not undergo programmed cell death but can continue to multiply without end.

This, in and of itself, disrupts the balance of cellular replication in the body. If one type of cell is allowed to replicate unchecked, it can supplant all others and undermine key biological functions. This is what happens with cancer and why these "immortal" cells can cause disease and death.

It is believed that cancer occurs because a genetic mutation can trigger the production of an enzyme, known as telomerase, which prevents telomeres from shortening.

While every cell in the body has the genetic coding to produce telomerase, only certain cells actually need it. Sperm cells, for example, need to the switch off telomere shortening in order to make more than 50 copies of themselves; otherwise, pregnancy could never occur.

If a genetic mishap inadvertently turns telomerase production on, it can cause abnormal cells to multiply and form tumors. It is believed that as life expectancy rates continue to grow, the chances of this occur will not only become greater but eventually become inevitable.

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The Relationship Between Telomeres, Aging, and Cancer

Get the brand new, comprehensive article I wrote on how sauna may affect longevity HERE: http://www.foundmyfitness.com/?sendme...

In this video Dr. Rhonda Patrick summarizes a recent study that found that frequency of sauna use was associated with decreased risk of death. Using the sauna 2-3 times per week was associated with 24% lower all-cause mortality and 4-7 times per week decreased all-cause mortality by 40%.

Rhonda discusses some possible mechanisms that could be responsible for the effect on longevity including the increased production of heat shock proteins (HSPs) and activation of the longevity gene, Foxo3. Heat stress increases the production of heat shock proteins, which prevent protein aggregation and protect against cardiovascular and neurodegenerative diseases. Heat stress also activates FOXO3, which activates many other genes that protect against the stress of aging including DNA damage, damage to proteins and lipids, loss of stem cell function, loss of immune function, cellular senescence and more.

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How Sauna Use May Boost Longevity - YouTube

Moles are very common, especially in people with fair skin. Moles are overgrowths of skin cells called melanocytes, but the genetic factors involved in their development are not well understood. Although moles, like tumors, are an overgrowth of cells, moles are almost always noncancerous (benign). Perhaps because most moles are benign, scientists have not studied them extensively, and not much is known about their genetics. Similar numbers of moles seem to occur on individuals of different generations of a family, so a tendency to develop moles seems to be inherited, but the inheritance pattern is not well understood.

Most moles occur on parts of the body that are exposed to the sun (ultraviolet radiation), and the number of moles an individual has may increase after extended time in the sun. Moles usually begin to occur in childhood. These moles are called acquired melanocytic nevi (and include the subtype epidermal nevus). It is common for new moles to appear during times when hormone levels change, such as adolescence and pregnancy. During an individuals lifetime, moles may change in appearance; hair may grow out of them, and they can change in size and shape, darken, fade, or disappear. Infants and the elderly tend to have the fewest moles.

Sometimes, moles are present at birth or develop during infancy. These moles, which are called congenital nevi, are almost always benign. Rarely, a very large mole, called a giant congenital melanocytic nevus, is present at birth. In rare cases, the most serious type of skin cancer (called melanoma) may develop in this type of mole.

Large, irregularly shaped and colored moles called dysplastic nevi or atypical moles can occur at any age. Although not common, they tend to be numerous, and they increase a persons risk of melanoma. Heredity contributes to the development of dysplastic nevi and to having a higher-than-average number of benign moles. Spending a lot of time in the sun can also increase the number of moles a person has. However, moles are often found on areas of the body that are not exposed, which suggests that factors other than ultraviolet radiation from the sun, perhaps hormones or other biologic processes, are involved in triggering the development of acquired melanocytic nevi and dysplastic nevi.

Although the genetics of melanoma has been widely studied, much less is known about genes involved in the development of benign moles. Variations in several genes, including FGFR3, PIK3CA, HRAS, and BRAF, are involved with benign moles. The most-studied of these is the BRAF gene. A mutation in BRAF leads to the production of an altered protein that causes melanocytes to aggregate into moles. This altered protein also triggers the production of a tumor-suppressor protein called p15 that stops moles from growing too big. In rare cases, BRAF mutations together with deletion of the CDKN2A gene causes a lack of p15, which creates the potential for mole cells to grow uncontrollably and become cancerous (malignant). The formation of cancer is increasingly likely when combined with environmental factors, such as cell damage caused by ultraviolet radiation exposure.

In susceptible individuals (those with fair skin, light hair, skin that burns instead of tans, a family history of melanoma, and genetic risk factors such as deletion of or mutations in the CDKN2A gene), ultraviolet radiation from repeated sun exposure can damage existing moles, increasing their risk of becoming malignant. Research has shown that individuals who have an abundance of moles are at an increased risk of melanoma. However, some people who are diagnosed with melanoma have few moles, and melanoma often develops in areas of the body that are not exposed to the sun. Researchers are working to identify additional susceptibility genes to better understand the genetics of moles and their relationship with cancer.

Plasmeijer EI, Nguyen TM, Olsen CM, Janda M, Soyer HP, Green AC. The natural history of common melanocytic nevi: a systematic review of longitudinal studies in the general population. J Invest Dermatol. 2017 Sep;137(9):2017-2018. doi: 10.1016/j.jid.2017.03.040. Epub 2017 May 18. PubMed: 28528913.

Roh MR, Eliades P, Gupta S, Tsao H. Genetics of melanocytic nevi. Pigment Cell Melanoma Res. 2015 Nov;28(6):661-72. doi: 10.1111/pcmr.12412. PubMed: 26300491. Free full-text available from PubMed Central: PMC4609613.

Silva JH1, S BC, Avila AL, Landman G, Duprat Neto JP. Atypical mole syndrome and dysplastic nevi: identification of populations at risk for developing melanoma - review article. Clinics (Sao Paulo). 2011;66(3):493-9. PubMed: 21552679. Free full-text available from PubMed Central: PMC3072014.

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Are moles determined by genetics? - Genetics Home ...

Sure, medical centers across the country have magnetic resonance imaging, or MRI, machines. But what makes the Health Nucleus MRI different?

First, in traditional medical care, its nearly impossible to get access to a whole body MRI without a significant medical reason. If you injure your knee, only your knee will be scanned in a standard medical MRI, for fear something else in the rest of the body may be seen or not seen and therefore opening the health system up for serious liability concerns.

At the Health Nucleus, we partner with you to take control of your health by actively enrolling in a whole body MRI, and we are equipped to review and interpret your entire scan to generate an unprecedented snapshot of your current health.

Protocols Not Available Anywhere Else

Without the use of contrast media that leaves many feeling nauseous, but whose purpose is to illuminate differences in the body, our MRIs secret sauce is found in our post-processing analysis.

Our proprietary software uncovers cancer, neurological, metabolic and cardiovascular concerns at their earliest stages when they can be addressed.

And unlike traditional medical care, our Health Nucleus is prides itself on a spa-like setting whose luxuries are on the level of our pioneering science. Our MRI techs take pride in ensuring your comfort and calmness in our MRI with guided meditation, aroma therapy, and audio-visual distraction should you wish.

Challenge your perspective on health. Learn how our Health Nucleus MRI might impact you and your health.

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Whole Body MRI Human Longevity, Inc.

There are several genes known as longevity genes that increase your odds of becoming a centenarian. Specific variants of these genes are associated with an increased likelihood of living to be 100 or more. And more importantly, these genetic variants are linked to longer healthspan.

What are the odds of living to 100?Someoneborn a hundred years ago has less than 1% chance of being alive today. If you are female and born in 1973, your odds of living to 100 are 20%. Wondering about the odds for your birth year? Here is a nice chart of your odds of living to 100 based on your birth year:http://discovertheodds.com/what-are-the-odds-of-living-to-100/

So if your odds of living to 100 are 20%, a gene that increases that by 1.5x or 2xis actually significant.Keep in mind, though, that while genetics does play a role in how long you live, there are other health and lifestyle factors that are also important. This is all about statistics here.

FOXO3A gene:

The FOXO3A gene (forkhead box O3) has been linked to longevity in several different studies. This gene is believed to regulate apoptosis, which is necessary for cell death, and is a tumor suppressor. One study describes it thus FOXO proteins have been involved in the regulation of response to oxidative stress, starvation and caloric restriction with the final effect of increasing lifespan and prevent aging-related diseases, such as diabetes and cancer[ref]For the SNP rs2802292, the G allele was found to be an indicator of longevity. The odds ratio of living longer for G/G vs. T/T was found to be 2.75 in a study of Japanese males. Another study of Italians found that a proxy of the SNP above is associated with a 1.5x increase in odds of longevity.

CETP Gene:Another gene related to longevity is the CETP gene (cholesteryl ester transfer protein) which is involved in exchanging triglycerides with cholesteryl esters. One polymorphism that is related to longevity is rs5882 (also referred to as I405V). The G allele is associated with a somewhat longer lifespan. Heterozygotes (A/G) and homozygotes (G/G) are more likely to have a longer lifespan and have higher HDL cholesterol. Homozygotes (G/G) also have a .28x lower risk of dementia and a .31x lower risk of Alzheimers! [study]

Check your 23andMe results for rs5882 (V.4, v.5):

IGF1R gene:The IGF1R gene codes for the insulin-like growth factor 1 receptor. IGF1 is a hormone that signals for growth and anabolic activities. Growth hormone levels generally fall as we age.

Carrying the genes that increase my chance of living to 100 has changed my attitude and way of thinking about getting older. First, planning for retirement is important! But even more on my mind is that the things that I do now to optimize my health will pay off in the long run with a longer healthspan. Prevention of Alzheimers Disease and optimizing my Circadian Rhythmare top on my list of lifehacks this year.

The OkinawanDiet is thought to promote healthy longevity in part through affecting FOXO3. The diet focuses on fresh vegetables, fish, lean meats, omega-3 fats, and unrefined carbohydrates.

Green tea polyphenols (EGC/G) have been found to increase FOXO3 levels.

Astaxanthin, naturally found in shrimp, salmon, and red algae, has been found to increase FOXO3 levels.[ref] If you arent getting enough astaxanthin from your diet, you can get it as a supplement.

More to read:

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Living to 100? Longevity and Genetics Genetic Lifehacks

Centenarian Daphne Brann, 110, exercising her right to vote!

The Genetics of Longevity Study

The Genetics of Longevity Study is an international survey of centenarians and their siblings. We examine potential genes they may have in common and other lifestyle factors that could influence the ability to achieve extreme old age. Participation involves health and family history questionnaires, as well as a small blood donation for the genetic aspect of the study. To enter the study we ask that the subject be 105+ years old. If the potential subject has living siblings, then a younger centenarian may be eligible.

Betty Colleran, 70, and mother Elizabeth Stanton, 100, together looking at family photographs.

The Genetics of Longevity Study: Offspring Study

The Genetics of Longevity Study: Offspring Study looks at children of centenarians and their spouses. We believe they may be a valuable group to study for genetic and environmental factors contributing to the ability to live to very old age in good health. We also enroll childrens spouses as a control group.

Dirk Struik, a leader in ethnomathematics, at his home at age 104.

The Genetics of Longevity Study: Neuropsychological Study

The Genetics of Longevity Study: Neuropsychological Study assesses cognitive function because we believe Alzheimers Disease is either markedly delayed, or even absent in some subjects. Approximately 30% of our subjects consent to donate their brains for detailed study after they have passed away.

If you or a family member(s) could be eligible to participate in one of our studies, please contact us.

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Studies New England Centenarian Study BUMC

The Biomedical Genetics Section is a cross-disciplinary team of clinicians, biostatisticians, genetic epidemiologists, molecular geneticists, and bioinformaticists working together to discover the links between complex human disease and genes.

The Biomedical Genetics faculty is presently directing projects involving multiple academic centers and private industry to identify genes for several complex diseases including age-related macular degeneration and Alzheimer disease. The Section is also actively involved in research projects in substance abuse, sickle cell disease, membranous nephropathy, mental illness, longevity, and the Framingham Heart Study. Cancer genetics, Epigenetics and developmental genetics are a major focus of our research labs.

As a part of the educational component of our programs mission, Biomedical Genetics offers a variety of opportunities for training leading to a Ph.D. in a genetics specialty including genetic epidemiology and molecular genetics. Our faculty teaches a variety of graduate level courses in medical genetics, genetics & genomics, genetic epidemiology, and addiction science on the Medical Campus.

For biomedical researchers both on campus and off, our programs Molecular Genetics Core Lab provides services for DNA and RNA extraction, sequencing, genotyping and cell line cultures.

Medical Genetics in the Post Genome Era

Recent advances in information technology, statistical genetic methodology, molecular genetics and bioinformatics, aided by funding for the human genome project, have heralded discoveries about the pathogenesis of many rare genetic conditions such as cystic fibrosis, Huntington disease, and Duchenne muscular dystrophy. These technologies have also furthered our understanding of common disorders including breast cancer, Alzheimer disease, and atherosclerosis through studies of families segregating classically inherited forms of these disorders. However, the genetic basis of common diseases is still enigmatic. The reasons for this include phenotypic and genetic diversity, and complex (and poorly understood) interactions between genes and the environment. These issues are addressable by studying very large and well characterized populations for a wide array of genetic and other risk factors. Successful performance of such studies requires skills and experience integrated from multiple disciplines including genetic epidemiology, biostatistics, molecular genetics, systems biology and information technology. The Biomedical Genetics Section brings together specialists in all of these areas who, through individual as well as highly collaborative research programs, are working to find genes modulating risk and expression of diseases and other human traits. These genes are potential diagnostic/predictive markers and therapeutic targets.

Biomedical Genetics Today

Presently, the Biomedical Genetics Section constitutes the largest concentration of human genetics research at either the Medical School or Charles River Campus at Boston University and is among the best funded and regarded in the country. Indeed, the increased awareness and need to understand the relationship between the approximately 26,000 human genes and susceptibility to disorders of public health concern (including infectious disease) is expressed in the current panoply of projects, spanning a rang of research from molecules to populations. Our research is funded by the National Institutes of Health, Veterans Administration, private industry and non-profit foundations, and includes the following areas:

We attract graduate students from a wide array of Masters and Ph.D programs throughout Boston University (e.g., molecular medicine, bioinformatics, epidemiology, genetics & genomics) to pursue dissertation research in our laboratories. Postdoctoral fellows find many opportunities for expanding technical skills and apprenticing for exciting careers in academic medicine and private industry. After you have browsed a bit, please feel free to contact any of the members of the faculty or trainees to get the inside story about our research and training programs or about our Information Technology capabilities and Molecular Genetics Core Laboratory services. We look forward to sharing out enthusiasm about our Section.

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Welcome to Biomedical Genetics - Boston University

The duration of human life (longevity) is influenced by genetics, the environment, and lifestyle. Environmental improvements beginning in the 1900s extended the average life span dramatically with significant improvements in the availability of food and clean water, better housing and living conditions, reduced exposure to infectious diseases, and access to medical care. Most significant were public health advances that reduced premature death by decreasing the risk of infant mortality, increasing the chances of surviving childhood, and avoiding infection and communicable disease. Now people in the United States live about 80 years on average, but some individuals survive for much longer.

Scientists are studying people in their nineties (called nonagenarians) and hundreds (called centenarians, including semi-supercentenarians of ages 105-109 years and supercentenarians, ages 110+) to determine what contributes to their long lives. They have found that long-lived individuals have little in common with one another in education, income, or profession. The similarities they do share, however, reflect their lifestylesmany are nonsmokers, are not obese, and cope well with stress. Also, most are women. Because of their healthy habits, these older adults are less likely to develop age-related chronic diseases, such as high blood pressure, heart disease, cancer, and diabetes, than their same-age peers.

The siblings and children (collectively called first-degree relatives) of long-lived individuals are more likely to remain healthy longer and to live to an older age than their peers. People with centenarian parents are less likely at age 70 to have the age-related diseases that are common among older adults. The brothers and sisters of centenarians typically have long lives, and if they develop age-related diseases (such as high blood pressure, heart disease, cancer, or type 2 diabetes), these diseases appear later than they do in the general population. Longer life spans tend to run in families, which suggests that shared genetics, lifestyle, or both play an important role in determining longevity.

The study of longevity genes is a developing science. It is estimated that about 25 percent of the variation in human life span is determined by genetics, but which genes, and how they contribute to longevity, are not well understood. A few of the common variations (called polymorphisms) associated with long life spans are found in the APOE, FOXO3, and CETP genes, but they are not found in all individuals with exceptional longevity. It is likely that variants in multiple genes, some of which are unidentified, act together to contribute to a long life.

Whole genome sequencing studies of supercentenarians have identified the same gene variants that increase disease risk in people who have average life spans. The supercentenarians, however, also have many other newly identified gene variants that possibly promote longevity. Scientists speculate that for the first seven or eight decades, lifestyle is a stronger determinant of health and life span than genetics. Eating well, not drinking too much alcohol, avoiding tobacco, and staying physically active enable some individuals to attain a healthy old age; genetics then appears to play a progressively important role in keeping individuals healthy as they age into their eighties and beyond. Many nonagenarians and centenarians are able to live independently and avoid age-related diseases until the very last years of their lives.

Some of the gene variants that contribute to a long life are involved with the basic maintenance and function of the bodys cells. These cellular functions include DNA repair, maintenance of the ends of chromosomes (regions called telomeres), and protection of cells from damage caused by unstable oxygen-containing molecules (free radicals). Other genes that are associated with blood fat (lipid) levels, inflammation, and the cardiovascular and immune systems contribute significantly to longevity because they reduce the risk of heart disease (the main cause of death in older people), stroke, and insulin resistance.

In addition to studying the very old in the United States, scientists are also studying a handful of communities in other parts of the world where people often live into their nineties and olderOkinawa (Japan), Ikaria (Greece), and Sardinia (Italy). These three regions are similar in that they are relatively isolated from the broader population in their countries, are lower income, have little industrialization, and tend to follow a traditional (non-Western) lifestyle. Unlike other populations of the very old, the centenarians on Sardinia include a significant proportion of men. Researchers are studying whether hormones, sex-specific genes, or other factors may contribute to longer lives among men as well as women on this island.

Martin GM, Bergman A, Barzilai N. Genetic determinants of human health span and life span: progress and new opportunities. PLoS Genet. 2007 Jul;3(7):e125. PubMed: 17677003. Free full-text available from PubMed Central: PMC1934400.

Sebastiani P, Gurinovich A, Bae H, Andersen S, Malovini A, Atzmon G, Villa F, Kraja AT, Ben-Avraham D, Barzilai N, Puca A, Perls TT. Four genome-wide association studies identify new extreme longevity variants. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1453-1464. doi: 10.1093/gerona/glx027. PubMed: 28329165.

Sebastiani P, Solovieff N, Dewan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Hoh J, Perls TT. Genetic signatures of exceptional longevity in humans. PLoS One. 2012;7(1):e29848. doi: 10.1371/journal.pone.0029848. Epub 2012 Jan 18. PubMed: 22279548. Free full-text available from PubMed Central: PMC3261167.

Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, Cohen P, Morgan TE, Dorff T, Hong K, Michalsen A, Laviano A, Longo VD. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017 Feb 15;9(377). pii: eaai8700. doi: 10.1126/scitranslmed.aai8700. PubMed: 28202779.

Young RD. Validated living worldwide supercentenarians, living and recently deceased: February 2018. Rejuvenation Res. 2018 Feb 1. doi: 10.1089/rej.2018.2057. [Epub ahead of print] PubMed: 29390945.

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Is longevity determined by genetics? - Genetics Home ...

The Longevity Illustrator calculates "Nearest Age" as the whole age you are closest to. For half the year, Nearest Age will be greater than your age on your last birthday. Please set your Illustration Age at least as great as your Nearest Age. If you leave the Illustration Age box blank, the tool automatically calculates longevity information from your Nearest Age. The Illustration Age will be rejected if it exceeds 99 or if the selection would cause Person 2 to be older than 99.

If you are already retired, or are considering retiring soon, you might choose to leave the Illustration Age box blank. However, if you expect to retire at a later date, or you are curious to know what your longevity might look like at some point in the future, you may enter a later age for the illustration to begin. In this case, the tool will assume you will survive to that later age.

For example, if your Nearest Age is 40 and you plan to retire at age 66, then entering age 66 as the age for the illustration to start will forecast results assuming you survive from now until age 66. The Longevity Illustrator allows you to experiment with different possibilities you might find interesting (if, for example, you are considering several different ages at which you might retire).

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Actuaries Longevity Illustrator - Enter Your Information

The Palo Alto Prize is a newly established Silicon Valley-based initiative of the Race Against Time Foundation. The mission of the Palo Alto Prize is to encourage collaboration, foster innovation, and build a community to address the underlying causes of aging.In addition to the $1 million of cash prizes, the Palo Alto Prize is also working with a number of angel investors, venture capital firms, corporate venture arms, institutions and private foundations to provide access to additional capital to the teams during the competition. While the Palo Alto Prize will help facilitate introductions, all transactions and due diligence will be done privately between the teams and potential investors and philanthropists.

The Race Against Time (dba The Hero Science Foundation http://www.herosf.org) is a 501(c)(3) educational non-profit organization (Tax ID: 47-2823482) created to raise public awareness and financial support for basic biomedical research related to increasing our health span and defining the fundamental biological mechanisms that prevent age-related diseases and disabilities.

About the prize sponsor:

Dr. Joon Yun, M.D., is the President of Palo Alto Investors, LLC, founded in 1989 with over $2 billion in assets under management invested in healthcare and the founder of the Palo Alto Institute, a nonprofit think-tank that has been providing operational support for the Palo Alto Prize. Board certified in radiology, Dr. Yun served on the clinical staff at Stanford Hospital from 2000-2006. Dr. Yun received his Bachelor of Arts in biology from Harvard University and his Doctor of Medicine from Duke University School of Medicine. Learn more at DrJoonYun.com and follow him at @drjoonyun

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Palo Alto Longevity Prize

In genetics, a mosaic, or mosaicism, involves the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg.[1][2] Mosaicism has been reported to be present in as high as 70% of cleavage stage embryos and 90% of blastocyst-stage embryos derived from in vitro fertilization.[3]

Genetic mosaicism can result from many different mechanisms including chromosome non-disjunction, anaphase lag, and endoreplication.[3] Anaphase lagging is the most common way by which mosaicism arises in the preimplantation embryo.[3] Mosaicism can also result from a mutation in one cell during development in which the mutation is passed on to only its daughter cells. Therefore, the mutation is only going to be present in a fraction of the adult cells.[2]

Genetic mosaics may often be confused with chimerism, in which two or more genotypes arise in one individual similarly to mosaicism. However, the two genotypes arise from the fusion of more than one fertilized zygote in the early stages of embryonic development, rather than from a mutation or chromosome loss.

Different types of mosaicism exist, such as gonadal mosaicism (restricted to the gametes) or somatic mosaicism.

Somatic mosaicism occurs when the somatic cells of the body are of more than one genotype. In the more common mosaics, different genotypes arise from a single fertilized egg cell, due to mitotic errors at first or later cleavages.

In rare cases, intersex conditions can be caused by mosaicism where some cells in the body have XX and others XY chromosomes (46, XX/XY).[4][5] In the fruit fly Drosophila melanogaster, where a fly possessing two X chromosomes is a female and a fly possessing a single X chromosome is a sterile male, a loss of an X chromosome early in embryonic development can result in sexual mosaics, or gynandropmorphs.[6][7] Likewise, a loss of the Y chromosome can result in XY/X mosaic males.[8]

The most common form of mosaicism found through prenatal diagnosis involves trisomies. Although most forms of trisomy are due to problems in meiosis and affect all cells of the organism, there are cases where the trisomy occurs in only a selection of the cells. This may be caused by a nondisjunction event in an early mitosis, resulting in a loss of a chromosome from some trisomic cells.[9] Generally this leads to a milder phenotype than in non-mosaic patients with the same disorder.

An example of this is one of the milder forms of Klinefelter syndrome, called 46/47 XY/XXY mosaic wherein some of the patient's cells contain XY chromosomes, and some contain XXY chromosomes. The 46/47 annotation indicates that the XY cells have the normal number of 46 total chromosomes, and the XXY cells have a total of 47 chromosomes.

Around 30% of Turner's syndrome cases demonstrate mosaicism, while complete monosomy (45, X) occurs in about 5060% of cases.

But mosaicism need not necessarily be deleterious. Revertant somatic mosaicism is a rare recombination event in which there is a spontaneous correction of a mutant, pathogenic allele.[10] In revertant mosaicism, the healthy tissue formed by mitotic recombination can outcompete the original, surrounding mutant cells in tissues like blood and epithelia that regenerate often.[10] In the skin disorder ichthyosis with confetti, normal skin spots appear early in life and increase in number and size over time.[10]

Other endogenous factors can also lead to mosaicism including mobile elements, DNA polymerase slippage, and unbalanced chromosomal segregation.[11] Exogenous factors include nicotine and UV radiation.[11] Somatic mosaics have been created in Drosophila using Xray treatment and the use of irradiation to induce somatic mutation has been a useful technique in the study of genetics.[12]

True mosaicism should not be mistaken for the phenomenon of Xinactivation, where all cells in an organism have the same genotype, but a different copy of the X chromosome is expressed in different cells. The latter is the case in normal (XX) female mammals, although it is not always visible from the phenotype (like it is in calico cats). However, all multicellular organisms are likely to be somatic mosaics to some extent.[13]

Somatic mutation leading to mosaicism is prevalent in the beginning and end stages of human life.[11] Somatic mosaics are common in embryogenesis due to retrotransposition of L1 and Alu transposable elements.[11] In early development, DNA from undifferentiated cell types may be more susceptible to mobile element invasion due to long, un-methylated regions in the genome.[11] Further, the accumulation of DNA copy errors and damage over a lifetime lead to greater occurrences of mosaic tissues in aging humans. As our longevity has increased dramatically over the last century, our genome may not have had time to adapt to cumulative effects of mutagenesis.[11] Thus, cancer research has shown that somatic mutations are increasingly present throughout a lifetime and are responsible for most leukemia, lymphomas, and solid tumors.[14]

One basic mechanism which can produce mosaic tissue is mitotic recombination or somatic crossover. It was first discovered by Curt Stern in Drosophila in 1936. The amount of tissue which is mosaic depends on where in the tree of cell division the exchange takes place. A phenotypic character called "Twin Spot" seen in Drosophila is a result of mitotic recombination. However, it also depends on the allelic status of the genes undergoing recombination. Twin spot occurs only if the heterozygous genes are linked in repulsion i.e. trans phase. The recombination needs to occur between the centromere the adjacent gene. This gives an appearance of yellow patches on the wild type background in Drosophila. another example of mitotic recombination is the Bloom's syndrome which happens due to the mutation in the blm gene. The resulting BLM protein is defective. the defect in RecQ an helicase facilitates the defective unwinding of DNA during replication and is thus associated with the occurrence of this disease.[15][16]

Germline or gonadal mosaicism is a special form of mosaicism, where some gametesi.e., sperm or oocytescarry a mutation, but the rest are normal.[17][18]

The cause is usually a mutation that occurred in an early stem cell that gave rise to all or part of the gametes.

This can cause only some offspring to be affected, even for a dominant disease.

Genetic mosaics can be extraordinarily useful in the study of biological systems, and can be created intentionally in many model organisms in a variety of ways. They often allow for the study of genes that are important for very early events in development, making it otherwise difficult to obtain adult organisms in which later effects would be apparent. Furthermore, they can be used to determine the tissue or cell type in which a given gene is required and to determine whether a gene is cell autonomous. That is, whether or not the gene acts solely within the cell of that genotype, or if it affects the entire organism of neighboring cells which do not themselves contain that genotype.

The earliest examples of this involved transplantation experiments (technically creating chimeras) where cells from a blastula stage embryo from one genetic background are aspirated out and injected into a blastula stage embryo of a different genetic background.

Genetic mosaics are a particularly powerful tool when used in the commonly studied fruit fly, where specially-selected strains frequently lose an X[7] or a Y[8] chromosome in one of the first embryonic cell divisions. These mosaics can then be used to analyze such things as courtship behavior,[7] female sexual attraction,[19] and the autonomy or non-autonomy of particular genes.

Genetic mosaics can also be created through mitotic recombination. Such mosaics were originally created by irradiating flies heterozygous for a particular allele with X-rays, inducing double-strand DNA breaks which, when repaired, could result in a cell homozygous for one of the two alleles. After further rounds of replication, this cell would result in a patch, or "clone" of cells mutant for the allele being studied.

More recently the use of a transgene incorporated into the Drosophila genome has made the system far more flexible. The flip recombinase (or FLP) is a gene from the commonly studied yeast Saccharomyces cerevisiae which recognizes "flip recombinase target" (FRT) sites, which are short sequences of DNA, and induces recombination between them. FRT sites have been inserted transgenically near the centromere of each chromosome arm of Drosophila melanogaster. The FLP gene can then be induced selectively, commonly using either the heat shock promoter or the GAL4/UAS system. The resulting clones can be identified either negatively or positively.

In negatively marked clones the fly is transheterozygous for a gene encoding a visible marker (commonly the green fluorescent protein or GFP) and an allele of a gene to be studied (both on chromosomes bearing FRT sites). After induction of FLP expression, cells that undergo recombination will have progeny that are homozygous for either the marker or the allele being studied. Therefore, the cells that do not carry the marker (which are dark) can be identified as carrying a mutation.

It is sometimes inconvenient to use negatively marked clones, especially when generating very small patches of cells, where it is more difficult to see a dark spot on a bright background than a bright spot on a dark background. It is possible to create positively marked clones using the so-called MARCM ("mosaic analysis with a repressible cell marker", pronounced [mark-em]) system, developed by Liqun Luo, a professor at Stanford University, and his post-doc Tzumin Lee who now leads a group at Janelia Farm Research Campus. This system builds on the GAL4/UAS system, which is used to express GFP in specific cells. However a globally expressed GAL80 gene is used to repress the action of GAL4, preventing the expression of GFP. Instead of using GFP to mark the wild-type chromosome as above, GAL80 serves this purpose, so that when it is removed by mitotic recombination, GAL4 is allowed to function, and GFP turns on. This results in the cells of interest being marked brightly in a dark background.[20]

In 1929, Alfred Sturtevant studied mosaicism in Drosophila.[6] A few years later, In the 1930s, Curt Stern demonstrated that genetic recombination, normal in meiosis, can also take place in mitosis.[21][22] When it does, it results in somatic (body) mosaics. These are organisms which contain two or more genetically distinct types of tissue.[23] The term "somatic mosaicism" was used by C.W. Cotterman in 1956 in his seminal paper on antigenic variation.[11]

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Mosaic (genetics) - Wikipedia

Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan.

The first mutation found to increase longevity in an animal was the age-1 gene in Caenorhabditis elegans. Michael Klass discovered that lifespan of C.elegans could be altered by mutations, but Klass believed that the effect was due to reduced food consumption (calorie restriction).[1] Thomas Johnson later showed that life extension of up to 65% was due to the mutation itself rather than due to calorie restriction,[2] and he named the gene age-1 in the expectation that other genes that control aging would be found. The age-1 gene encodes the catalytic subunit of class-I phosphatidylinositol 3-kinase(PI3K).

A decade after Johnson's discovery daf-2, one of the two genes that are essential for dauer larva formation,[3] was shown by Cynthia Kenyon to double C.elegans lifespan.[4] Kenyon showed that the daf-2 mutants, which would form dauers above 25C (298K; 77F) would bypass the dauer state below 20C (293K; 68F) with a doubling of lifespan.[4] Prior to Kenyon's study it was commonly believed that lifespan could only be increased at the cost of a loss of reproductive capacity, but Kenyon's nematodes maintained youthful reproductive capacity as well as extended youth in general. Subsequent genetic modification (PI3K-null mutation) to C.elegans was shown to extend maximum life span tenfold.[5][6]

Genetic modifications in other species have not achieved as great a lifespan extension as have been seen for C.elegans. Drosophila melanogaster lifespan has been doubled.[7] Genetic mutations in mice can increase maximum lifespan to 1.5times normal, and up to 1.7times normal when combined with calorie restriction.[8]

In yeast, NAD+-dependent histone deacetylase Sir2 is required for genomic silencing at three loci: the yeast mating loci, the telomeres and the ribosomal DNA (rDNA). In some species of yeast, replicative aging may be partially caused by homologous recombination between rDNA repeats; excision of rDNA repeats results in the formation of extrachromosomal rDNA circles (ERCs). These ERCs replicate and preferentially segregate to the mother cell during cell division, and are believed to result in cellular senescence by titrating away (competing for) essential nuclear factors. ERCs have not been observed in other species (nor even all strains of the same yeast species) of yeast (which also display replicative senescence), and ERCs are not believed to contribute to aging in higher organisms such as humans (they have not been shown to accumulate in mammals in a similar manner to yeast). Extrachromosomal circular DNA (eccDNA) has been found in worms, flies, and humans. The origin and role of eccDNA in aging, if any, is unknown.

Despite the lack of a connection between circular DNA and aging in higher organisms, extra copies of Sir2 are capable of extending the lifespan of both worms and flies (though, in flies, this finding has not been replicated by other investigators, and the activator of Sir2 resveratrol does not reproducibly increase lifespan in either species.[9]) Whether the Sir2 homologues in higher organisms have any role in lifespan is unclear, but the human SIRT1 protein has been demonstrated to deacetylate p53, Ku70, and the forkhead family of transcription factors. SIRT1 can also regulate acetylates such as CBP/p300, and has been shown to deacetylate specific histone residues.

RAS1 and RAS2 also affect aging in yeast and have a human homologue. RAS2 overexpression has been shown to extend lifespan in yeast.

Other genes regulate aging in yeast by increasing the resistance to oxidative stress. Superoxide dismutase, a protein that protects against the effects of mitochondrial free radicals, can extend yeast lifespan in stationary phase when overexpressed.

In higher organisms, aging is likely to be regulated in part through the insulin/IGF-1 pathway. Mutations that affect insulin-like signaling in worms, flies, and the growth hormone/IGF1 axis in mice are associated with extended lifespan. In yeast, Sir2 activity is regulated by the nicotinamidase PNC1. PNC1 is transcriptionally upregulated under stressful conditions such as caloric restriction, heat shock, and osmotic shock. By converting nicotinamide to niacin, nicotinamide is removed, inhibiting the activity of Sir2. A nicotinamidase found in humans, known as PBEF, may serve a similar function, and a secreted form of PBEF known as visfatin may help to regulate serum insulin levels. It is not known, however, whether these mechanisms also exist in humans, since there are obvious differences in biology between humans and model organisms.

Sir2 activity has been shown to increase under calorie restriction. Due to the lack of available glucose in the cells, more NAD+ is available and can activate Sir2. Resveratrol, a stilbenoid found in the skin of red grapes, was reported to extend the lifespan of yeast, worms, and flies (the lifespan extension in flies and worms have proved to be irreproducible by independent investigators[9]). It has been shown to activate Sir2 and therefore mimics the effects of calorie restriction, if one accepts that caloric restriction is indeed dependent on Sir2.

According to the GenAge database of aging-related genes, there are over 1800 genes altering lifespan in model organisms: 838 in the soil roundworm (Caenorhabditis elegans), 883 in the bakers' yeast (Saccharomyces cerevisiae), 170 in the fruit fly (Drosophila melanogaster) and 126 in the mouse (Mus musculus).[10]

The following is a list of genes connected to longevity through research [10] on model organisms:

Ned Sharpless and collaborators demonstrated the first in vivo link between p16-expression and lifespan.[11] They found reduced p16 expression in some tissues of mice with mutations that extend lifespan, as well as in mice that had their lifespan extended by food restriction. Jan van Deursen and Darren Baker in collaboration with Andre Terzic at the Mayo Clinic in Rochester, Minn., provided the first in vivo evidence for a causal link between cellular senescence and aging by preventing the accumulation of senescent cells in BubR1 progeroid mice.[12] In the absence of senescent cells, the mices tissues showed a major improvement in the usual burden of age-related disorders. They did not develop cataracts, avoided the usual wasting of muscle with age. They retained the fat layers in the skin that usually thin out with age and, in people, cause wrinkling. A second study led by Jan van Deursen in collaboration with a team of collaborators at the Mayo Clinic and Groningen University, provided the first direct in vivo evidence that cellular senescence causes signs of aging by eliminating senescent cells from progeroid mice by introducing a drug-inducible suicide gene and then treating the mice with the drug to kill senescent cells selectively, as opposed to decreasing whole body p16.[13] Another Mayo study led by James Kirkland in collaboration with Scripps and other groups demonstrated that senolytics, drugs that target senescent cells, enhance cardiac function and improve vascular reactivity in old mice, alleviate gait disturbance caused by radiation in mice, and delay frailty, neurological dysfunction, and osteoporosis in progeroid mice. Discovery of senolytic drugs was based on a hypothesis-driven approach: the investigators leveraged the observation that senescent cells are resistant to apoptosis to discover that pro-survival pathways are up-regulated in these cells. They demonstrated that these survival pathways are the "Achilles heel" of senescent cells using RNA interference approaches, including Bcl-2-, AKT-, p21-, and tyrosine kinase-related pathways. They then used drugs known to target the identified pathways and showed these drugs kill senescent cells by apoptosis in culture and decrease senescent cell burden in multiple tissues in vivo. Importantly, these drugs had long term effects after a single dose, consistent with removal of senescent cells, rather than a temporary effect requiring continued presence of the drugs. This was the first study to show that clearing senescent cells enhances function in chronologically aged mice.[14]

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Genetics of aging - Wikipedia

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Further Reading

Andersen SL, Sebastiani P, Dworkis DA, Feldman L and Perls TT (2012) Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span. Journals of Gerontology Series A, Biological Sciences and Medical Sciences 67: 395405.

Chang AL, Bitter PH Jr., Qu K et al. (2013) Rejuvenation of gene expression pattern of aged human skin by broadband light treatment: a pilot study. Journal of Investigative Dermatology 133: 394402.

Chung WH, Dao RL, Chen LK and Hung SI (2010) The role of genetic variants in human longevity. Ageing Research Reviews 9 (Suppl 1): S67S78.

Kahn AJ (2014) FOXO3 and related transcription factors in development, aging, and exceptional longevity. Journals of Gerontology Series A, Biological Sciences and Medical Sciences. doi: 10.1093/gerona/glu044 (Epub ahead of print).

LabatRobert J and Robert L (2014) Longevity and aging. Role of free radicals and xanthine oxidase. A review. PathologieBiologie 62: 6166.

Raichlen DA and Alexander GE (2014) Exercise, APOE genotype, and the evolution of the human lifespan. Trends in Neurosciences 37: 247255.

Rajpathak SN, Liu Y, BenDavid O et al. (2011) Lifestyle factors of people with exceptional longevity. Journal of the American Geriatrics Society 59: 15091512.

Seripa D, D'Onofrio G, Panza F et al. (2011) The genetics of the human APOE polymorphism. Rejuvenation Research 14: 491500.

Sevini F, Giuliani C, Vianello D et al. (2014) mtDNA mutations in human aging and longevity: controversies and new perspectives opened by highthroughput technologies. Experimental Gerontology 56: 234244.

Zhu H, Belcher M and van der Harst P (2011) Healthy aging and disease: role for telomere biology? Clinical Science 120: 427440.

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Genetics and Genomics of Human Longevity

Senescent cell removal135%2016Does not affect rotarod performance, object discrimination. Slight delay in wound closure.1Rapamycin110%2009Late-life rapamyicn treatment extends lifespan (pooled females from multiple-site NIA study)2NR105%2016Claim an increase in running distance3Catalase117%2005Mitochondrially-targeted catalase expression extended mouse lifespan compared to control4Sirt6 overexpression115%2012Sirt6-overexpression increases male mouse lifespan5Metformin106%2013In males, small but significant lifespan extension after metformin application6DN-IB110%2013Dominant negative to downregulate IKK-beta activity, delivered to hypothalamus of middle-aged mice7Klotho120%2005Overexpression under human elongation factor 1 promoter increases lifespan, slight fertility loss8S6K1118%2009KO of S6K1 extends lifspan compared to wildtype mice9p66128%1999Mutation of a p66shc, member of proto-oncogene locus SHC, extends lifespan. May be just due to cancer effect.10Lowering protein:carbohydrate ratio128%2014Varied protein, carbohydrate, and total energy levels.11Fat-specific insulin receptor knockout mice111%2003Fat-specific insulin receptor knockout mice show a significant increase in lifespan12C57BL/6 mice with NZB/OlaHsd mitochondrial mutations120%2016Same nuclear, different mitochondrial DNA.13Fasting mimicking diet112%2015FMD followed by 10 days of normal, then repeat14Rapamycin127%2014Rapamycin from 9 months of age, weight decreased ~30% at highest dose15Brain-specific Sirt1 expression116%2013Brain-specific Sirt1 expression in female mice increases lifespan over wildtype16SRT1720104%2014Start diet at 28 weeks of age, very small increase on lifespan17Spermidine111%2016Polyamine, administered in drinking water18Atg5 overexpression117%2013Transgenic mice ubiquitously expressing Atg5 (crucial for autophagasome confirmation) live longer.19Telomerase124%2012Paper showing telomerase therapy increasing life20Insulin receptor substrate null132%2008Insulin receptor substrate 1 null mouse lifespan extension in females21Snell Dwarf Mice142%2001Snell dwarf mouse paper showing life extension22Ames Dwarf Mice168%1996Original Ames dwarf mouse paper showing life extension23s-Arf/p53113%2007An extra copy of p53 and upstream regulator Arf/p16Ink4a increases lifespan24Slow growth during lactation106%2004Male mice suckled by dams fed a low-protein diet lived longer than their control cohort25Methionine restriction111%2005Methionine restriction increases mouse lifespan, here median lifespan increase in mice that survived at least 1 yr.26Rapamycin (3 months)114%2016Lifespan given from time of treatment which was 23-24 mo, used 24 mo to get percentage so this is an estimate27GHR-BP138%2000Mice deficient in growth hormone receptor / binding protein live longer (female mean, not median, lifespan shown here)28mTOR116%2013mTOR depletion extends lifespan29PTEN overexpression112%2012Overexpression of PTEN, a tumor suppressor which counteracts PI3K, extends mouse lifespan30Myc (+/-)121%2015Claim no correlation between weight and lifespan31FGF-21139%2012Hepatic-specific expression of FGF-21 (which suppresses growth hormone and reduces the production of IGF) increases lifespan, female lifespan shown here32BubR1 overexpression114%2012Kinase which localizes to kinetochore, overexpression increases lifespan33AC5 KO132%2007AC5 knockount mice lived longer than control, potentially linked to effects on cAMP production and beta-adrenergic receptor signaling.3417-alpha-estradiol112%201317-alpha-estradiol extended lifespan in males, but not females (as expected)35Acarbose122%2013Acarbose extended male more than female lifespan36TRPV1 -/-114%2014Resting exchange ratio similar at 16 mo to 3 mo37SRT2104106%2014Start diet at 28 weeks of age, very small increase if there38Hcrt-UCP2128%2006UCP2 under hypocretin promoter lowers core body temp, increases lifespan39G6PD overexpression114%2016Reduces NADP+40IGF-1 Receptor Brain KO (+/-)109%2008Brain-specific IGF-1 Receptor +/- mice live longer than WT41SURF-1 KO121%2007Mutations in SURF1, a cytochrome c oxidase assembly factor, extend lifespan. Mitochondrial.42Litter enlargemnet (CR)118%200950% enlargement of litter in first 20 days, to induce caloric restriction43mclk-1 heterozygous115%2005A heterozygous knockout of mclk1 (important in mitochondrial respiration) results in mouse lifespan extension compared to wildtype44Nordihydroguairaitic acid112%2008NDGA and aspirin extend lifespan by a little bit. Small molecule.45Aspirin108%2008NDGA and aspirin extend lifespan by a little bit. Small molecule.46SOD mimetic carboxyfullerene115%2008Carboxyfullerene, described as an SOD mimetic, increased the lifespan of treated mice compared to wildtype control47Removal of visceral fat tissue108%2008Removal of visceral fat tissue increases lifespan over control48Low glycotoxin diet112%2007Low glycotoxin (low levels of AGE's) shown to extend lifespan49Per2 (-/-)118%2016Lifespan study incomplete50Neonatal metformin120%2015Animals recieved on 3, 5, 7th day after birth - bad for females, good for males.51GHRH KO146%2013GHRH (Growth-Hormone Releasing Hormone) disruption extends lifespan, presumably through the insulin/IGF pathway axis52Sod-2 overexpresion104%2007Overexpression of SOD-2 targeted to the mitochondrion increases mouse lifespan relative to wildtype53Metallothionein cardiac-specific expression114%2006Cardiac-specific expression of antioxidant metallothionein extended the lifespan of wildtype mice compared to WT FVB control.54IGF1R(+/-)121%2013Tyrosine kinase receptor activated by IGF1/255Ink4a/Arf/Ink4b116%2009Encodes 2 CDKs (p16 and p15), and Arf (upstream of p53)56Adult-onset Ghr (-/-)100%2016Male mice have >2x higher insulin than female mice57Ovary Transplantation117%2003Original paper showing that transplantation of young ovaries into old animals could result in lifespan increase58UCP-1 transgenic111%2007Transgenic mice with skeletal muscle-specific UCP1 had increased longevity. Small increase if there.59PAPP131%2010Knockout of PAPP-A (which enhances IGF-1 activity by degrading the inhibitory IGF-binding protein) increases lifespan over wildtype, female lifespan shown here60CR diet with lard132%201540% decrease starting at 4 months61loss of function of Riib (PKA subunit)114%2009Knockout of RIIbeta, a subunit of PKA, increased lifespan in mice compared to wildtype62Myostatin (+/-)109%2015Knockout induces double-muscle mice63Akt1 +/-113%2013Haploinsufficiency of Akt1 increases mouse lifespan relative to wildtype. Insulin/IGF-1 pathway.64miR-17117%2014Not clear if there is a main function for miR-1765NDGA111%2015Makes up ~12.5% of the dry weight of leaves66FAT10ko119%2014Ubiquitin-like protein which can signal for protein to go to proteasome.67Intranasal Hsp70116%2015Seemed to extend lifespan when started at 17 months68RasGRF1(-/-)120%2011Ras-guanine nucleotide exchange factor (Ras-GRF1) -/- mice displayed increased lifespan compared to wildtype.69Lmna-Lcs (Lamin C alone)113%2014Body weight and tumor incidence increase in mice expressing only Lamin-C70Cisd2 overexpression119%2011Cisd2 transgenic mice (expressing more of it) lived longer than wildtype. Cisd2 is a transmembrane protein expressed on the mitochondrial outer membrane and associated with a human longevity locus.71metoprolol110%2013Administration of the beta-adrenerginc receptor blocker metoprolol to mice increased lifespan compared to wildtype72nebivolol106%2013Administration of the beta-adrenerginc receptor blocker nebivolol to mice increased lifespan compared to wildtype73uPA (in ocular lens/CNS nerve cells)118%1997uPA expression under alpha-crystallin promoter increases lifespan, small/eat less74MIF-1 KO116%2010MIF-1 knockout mutant (T-cell derived cytokine) extends lifespan75mGsta4-null113%2009Enzyme protects against lipid peroxidation, weird that less of its activity might increase lifespan76Muscle-specific GHRKO109%2015Knockout under muscle creatinine kinase promoter77CAM-(1A)AR mice110%2011Mice with a constitutively active mutant form of the alpha1-adrenergic receptor (CAM-alpha1aAR) lived longer than wildtype control78Cardiac-specific catalase overexpression113%2007Overexpression of catalase specifically in the heart in mice79Icariin108%2015Flavonoid80miR-29 brain-specific KO112%2016miR-29 highly expresed in brain during development81Bi-maternal mice128%2010Mice prepared to be bi-maternal were found longer-lived than their normal cohort82RNase-L(-/-)127%2007Knockout of RNase-L, which accelerates cell senescence when expressed, increases lifespan in mice compared to wildtype83hMTH1-Tg116%2013Express high levels of hMTH1 hydrolase, thought to degrade 8-oxodGTP and 8-oxoGTP. Oxidative stress.84DGAT-1 -/-126%2012Knockout of DGAT1, which catalyzes triglyceride synthesis, extends mouse lifespan relative to wildtype85IGFBP-2 overexpression105%2016Proteins bind IGF1/2, degraded during pregnancy, delay in sexual maturity86PAPP-A on high-fat diet105%2015Males chosen so no adverse developmental effect on fat depots87clk-1(-/-) with clk-1 transgene128%2014clk-1 functions in ubiquinone synthesis, but levels weren't very affected.88AgRP -/-110%2006Neuropeptide that is appetite stimulator, overexpression leads to hyperphagia and obesity.89Bone marrow transplantation106%2013Bone marrow transplantation from young to old mice was claimed to extend lifespan90Young blood injections94%2014Resulted in decreased lifespan91Nas(-/-) mice125%2011Hyposulfatemic NaS1 null mice (Nas1 -/-) had an increased lifespan compared to wildtype control.92Cyclophilin D (+/-)119%2017Decrease in maximum lifespan93PAPP-A in adults120%2017Tamoxifen-induced knockdown94Mtbp (+/-)120%2016Rotarod, open field, blood glucose, insulin, IGF-1 were the same.95

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Longevity FAQ Laura Deming