StemCell Therapy

Nearly every adult would like to look and feel younger. Many adults would even like to completely stop the aging process all together. Transformations has not yet found a way to totally stop the aging process but has found and is now offering a Safe and Effective way to start the rejuvenating process in a very affordable way. It is called Sermorelin.

What is Sermorelin?

Sermorelin is a synthetic hormone that has been proven to aid in raising levels of hGH, Human Growth Hormone. As we all know, time goes on and we begin to experience the loss of physical and mental capabilities simply due to the nature of aging. Transformations is ableprovide the aging male and female an option to look and feel like they are still in their prime.

What is hGH? Human Growth Hormone (hGH)therapyhas been used for many years, and was effective for thousands of patients worldwide. HGH therapy is the direct injection of synthetic hGH, which does increase the bodies level, however it can come with side effects long-term. Side effects may include shutting down the pituitary glands natural production or hypoglycemia in some cases. Sermorelin solved these issues.

How Sermorelin Works: Sermorelin Therapyachieves the benefits associated with higher Growth Hormone levels but without side effects. Sermorelin attacks the cause of declining hGH by naturally stimulating the pituitary gland to produce more hGH at night while you sleep. This natural stimulation of the pituitary sustains and elevates the production of Growth Hormone mechanisms that decline as we age.

1. Increased structural integrity of bones with improved calcium retention 2. Improved quality of sleep predicated by increased REM Sleep 3. Boosted immune health

4. Higher levels of stamina 5. Improved muscle strength 6. Thicker, fuller hair 7. Enhanced emotional health with increased vitality and energy

8. Improved cardiac function 9. Speedier physical rehabilitation from surgery and injury

10. Increased metabolism which burns adipose fat 11. Smoother, tighter skin 12. Increased muscle mass 14. Enhanced libido and restored sexual ability 15. Improved cognition 16. Enhanced renal functionType your paragraph here.

Sermorelin: Transformations' NewFountain of Youth Injection

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Sermorelin Injections - Go Daddy Software

At Advanced Orthopedics & Sports Medicinewe pride ourselves in providing the most up to date medical procedures in the practice advanced orthopedics and sports related medicine - also known as sport and exercise medicine - dealing with the treatment and prevention of injuries related to playing various sports and other activities. These can be anything from concussions, muscle cramps, to ACL sprains, ACL tears, Ankle Sprain, Shin Splints as well as muscle strains and much more.

We provide top quality treatment for children as well as seniors in the areas of general orthopedic and sports medicine injury care as well as specialty care in the ranges of spine care, pain management, knee, foot & ankle care, hand and upper extremity care, shoulder care, rheumatology, fractures, trauma care, minimally invasive surgery of all areas of chronic pain, rheumatic diseases, musculoskeletal injuries and arthritis, cartilage transplantation.

We fully understand that each individual requires a personalized evaluation and treatment plan tailored to his or her specific needs. Our physicians, known to be in the top of their respective fields, are especially proud of our goal which is to provide the best medical care possible for you our patient - this is our number one priority. Through our commitment to advanced orthopedic care methods we strive to build open, honest and trusting relationships with all of our patients and in so doing we will continue to strive to uphold our enviable reputation for the best in orthopedic and sports medicine care in the Las Vegas and surrounding communities. We strive to help our patients return to a healthy and active lifestyle by offering a wide range of treatment options, including both orthopedic surgery and minimally invasive surgery and non-surgical treatments.

An excellent medical clinic is defined only by the quality of its doctors, nurses and staff. At Advanced Orthopedics and Sports Medicine we pride ourselves on an excellent, hand-picked staff that includes qualified orthopedic surgeons, nurses and a staff that meets and exceeds the highest board certified standards of medical excellence which leads to a unparalleled level of orthopedic care as well as peace of mind for all of our patients. It's your assurance that your medical treatment is being provided by the finest doctors.

Our orthopedic care physicians, surgeons and Knee Specialists include; Dr. X. Nick Liu, Dr. Timothy J. Trainor, Dr. Randall E. Yee, Dr. Thomman Kuruvilla, Dr. Sep Bady, Dr. Matthew Otten and Dr. Michael Trainor and their staff dedicate their time and talents daily to assure every patient need is met. This extremely qualified staff of doctors and surgeons are experts in their respective fields. They are highly skilled in a wide range of advanced orthopedic specialties to meet your medical needs.

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Sports Medicine Las Vegas - Advanced Orthopedics & Sports ...

Nanomedicine Overview

What if doctors had tiny tools that could search out and destroy the very first cancer cells of a tumor developing in the body? What if a cell's broken part could be removed and replaced with a functioning miniature biological machine? Or what if molecule-sized pumps could be implanted in sick people to deliver life-saving medicines precisely where they are needed? These scenarios may sound unbelievable, but they are the ultimate goals of nanomedicine, a cutting-edge area of biomedical research that seeks to use nanotechnology tools to improve human health.

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A lot of things are small in today's high-tech world of biomedical tools and therapies. But when it comes to nanomedicine, researchers are talking very, very small. A nanometer is one-billionth of a meter, too small even to be seen with a conventional lab microscope.

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Nanotechnology is the broad scientific field that encompasses nanomedicine. It involves the creation and use of materials and devices at the level of molecules and atoms, which are the parts of matter that combine to make molecules. Non-medical applications of nanotechnology now under development include tiny semiconductor chips made out of strings of single molecules and miniature computers made out of DNA, the material of our genes. Federally supported research in this area, conducted under the rubric of the National Nanotechnology Initiative, is ongoing with coordinated support from several agencies.

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For hundreds of years, microscopes have offered scientists a window inside cells. Researchers have used ever more powerful visualization tools to extensively categorize the parts and sub-parts of cells in vivid detail. Yet, what scientists have not been able to do is to exhaustively inventory cells, cell parts, and molecules within cell parts to answer questions such as, "How many?" "How big?" and "How fast?" Obtaining thorough, reliable measures of quantity is the vital first step of nanomedicine.

As part of the National Institutes of Health (NIH) Common Fund [nihroadmap.nih.gov], the NIH [nih.gov] has established a handful of nanomedicine centers. These centers are staffed by a highly interdisciplinary scientific crew, including biologists, physicians, mathematicians, engineers and computer scientists. Research conducted over the first few years was spent gathering extensive information about how molecular machines are built.

Once researchers had catalogued the interactions between and within molecules, they turned toward using that information to manipulate those molecular machines to treat specific diseases. For example, one center is trying to return at least limited vision to people who have lost their sight. Others are trying to develop treatments for severe neurological disorders, cancer, and a serious blood disorder.

The availability of innovative, body-friendly nanotools that depend on precise knowledge of how the body's molecular machines work, will help scientists figure out how to build synthetic biological and biochemical devices that can help the cells in our bodies work the way they were meant to, returning the body to a healthier state.

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Last Updated: January 22, 2014

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Nanomedicine Fact Sheet - Genome.gov | National Human ...

Adipose Stem Cell Therapy

What is an Autologous Adipose Stem Cell Procedure?

A small sample of Adipose tissue (fat) is removed from above the Superior Iliac spine (love handles) or abdomen under a local anesthetic.

Obtaining Adipose-Derived Stem Cells (ADSCs) is much easier and less invasive than performing abone marrowextraction. In addition, adipose tissue contains much larger volumes of mesenchymal stem cells than does bone marrow. We use the patient's own adipose tissue to extract the stem cells. Autologous meansthat the donor and the recipient are the same person.

Benefits of ADSCs: Stem cells play an integral part in wound healing and regeneration of tissue at the cellular level.

The Major Advantages of Adipose Stem Cell Therapy:

Is this procedure a significant improvement on other treatments currently available?

Yes We can now obtain Adult Stem Cells (ASCs) from a fat sample. This in-clinic treatment is completed the same day, and there is no need to ship samples to an outside laboratory and wait days for the cells to be returned for an injection on a second visit. This faster process provides increased stem cell counts, without manipulation.

Is an Autologous Adipose Stem Cell Procedure Safe?

Yes because the adipose tissue is removed from one's own body via sterile technique and remains in a controlled environment there are no problems with cell rejection or disease transmission. The interview, physical, harvesting, and administration of stem cells are all performed in-house under a physicians control.

How do I know if stem cell therapy is right for me?

Discussing treatment options with your physician is an important first step in making a decision regarding stem cell therapy. Potential outcomes, an integrative and comprehensive treatment plan, and financial costs are all factors to consider.

I have heard Stem Cell Treatments are VERY expensive, can I afford this?

Yes you can!

Due to our advanced adult stem cell technology provided in the form of an in house procedure, our Stem Cell Center can now provide this service at a fraction of the cost previously incurred. Even better, its a same day procedure.We offer theentirety of our treatment in Phoenix, Arizona -USA and we have been able to lower our cost to a flat rate of $7,100.00 per treatment (including consultation). Fees are subject to change and some more complex proceduresmay incur additional costs.

Why Choose an Adipose Stem Cell Procedure?

Adipose-derived mesenchymal stem cells areeasier to harvest than bone marrowand can be obtained in much larger quantities. In addition, it is much less painful and involves lower risks.

*There is a much shorter time from extraction to the administration oftreatment.No culturing or manipulation is needed using our procedure, as opposed to a bone marrow extraction which requires days or weeksto reach the necessary therapeutic threshold.

*There are no ethical or moral issues involved in harvesting autologous Adult Stem Cells (ASCs).

Are There Detrimental Side Effects from an Adipose Stem Cell Procedure?

No, the adipose tissue is extracted from the patients own body sono foreign donors are used. This minimizes the potential for immune rejection.Our procedure is performed completely in-house and administered by licensed physicians here in the United States. Please keep in mind that every procedure does have its risks, but we do practice sterile technique which makes the risk of infectionvery low.In fact, we have not had any infections develop in any of the stem cell patients we have treated as we take great care in keeping a sterile environment.

What You Can Expect When Visiting the Stem Cell Rejuvenation Center:

Differences Between An Adipose And A Bone Marrow Procedure:

Autologous Growth Factor Components of PRP:

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About Adipose Stem Cell Therapy

The University of Michigan is committed to the thoughtful and compassionate combination of complementary therapies and conventional medicine through the activities of research, education, clinical services and community partnerships.

We offer our patients the following services:

We provide primary care services for the whole family focusing on integrative medicine, anthroposophic medicine and holistic medicine. An integrative medicine plan is created that suits each individual's unique needs, offering specific recommendations for mind, body, spirit and emotion that optimize health. Integrative therapies such as holistic nutrition, relaxation techniques, acupuncture, massage, herbs and supplements are blended with the best of medical science and technology.

Holistic medicine is the art and science that addresses the whole person and uses both conventional and complementary therapies to prevent and treat disease, but most importantly to promote optimal health. Holistic physicians work together to transform health care to integrate all aspects of well being, including physical, environmental, mental, emotional, spiritual and social health, thereby contributing to the healing of ourselves and of our planet.

Anthroposophic medicine views health as a matter of balancing the mind, body, and spirit. It is centered on the idea that human beings are composed of the interactions of physical body, inner life body, mind, emotions and self-awareness.

At the University of Michigan, we investigate the use of complementary alternative medicine therapies in the prevention, management and treatment of conditions such as heart disease, diabetes, cancer and rheumatologic disorders. Alternative therapies investigated include acupuncture, nutrition, herbal medicine, spirituality, mind-body therapies, and energy medicine. Lifestyle change programs that include stress reduction and respite in nature are also actively researched.

To make an appointment, please call 734-998-7390.

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Integrative Medicine | University of Michigan Health System

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CentreSpring MD | Atlanta Holistic & Integrative Medicine

Welcome

Thank you for visiting CIM. As the the fastest growing leader in on-line Integrative Medicine education today, CIM is committed to helping doctors expand their practices and move them toward becoming the primary integrative medicine practitioner in their community. Earning an integrative medicine certification has never been more convenient or universal in scope. We do more than just teach integrative medicine. We show our doctors how to apply it in practice.

CIM's program is the most cost effective comprehensive integrative medicine program available that includes the functional medicine component. Unlike comparable programs that average $31K - $53K, there are no holding fees, application fees, or otherwise hidden costs. We understand the expenses of running a practice so we offer affordable interest free payment plans of 6 or 12 months. Learning on-line means that you don't have to close your practice, pay for airfare, hotels, or other expenses. You control when you learn based on without worry about completion deadlines with 24/7 unlimited access.

All students receive a free subscription ($540 annual value) to CIM's Clinical Reference Library which is packed with hundreds of treatment protocols, interactive patient management tools, case presentations, and more. We also provide a one year paid subscription to IMCJ (Integrative Medicine: A Clinician's Journal).

CIM is an approved continuing education provider for the American Clinical Board of Nutrition (accredited through the National Commission for Certifying Agencies). Earn your Certified Integrative Health Care Practitioner Certification through CIM and your Diplomate in Nutrition from the ACBN. Continuing Education is applied for through National University of Health Sciences for DCs. Applications are pending for CE of other disciplines.

For more information on the American Clinical Board of Nutrition Diplomate Board Examination requirements visit: http://www.ACBN.org

(Click onto the course name or visit the Courses link for detailed program information)

Open Enrollment. Being Immediately

"I had the privilege of being a student of Dr.Sodano during my postgraduate diplomat in internal medicine and would always look forward to his lectures. Dr. Sodano has a genuine concern for our profession and for his students to be able to stand "Toe to Toe" as I remember the late Dr. Kessinger often said. The course of instruction can be overwhelming but Dr. Sodano brought application from his experience as a practicing physician to his instruction. We are fortunate in our profession to have the dedication of extremely capable physicians like Dr.Sodano that continue to sacrifice their time and efforts to others. ~ Dean Kenny, DC, DABCI

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College of Integrative Medicine | Home

All users must read and agree to our Terms of Service before using this feature.

Fill in ANY one or more of the fields below and press the search button to locate physicians.

In order to optimize your ability to find a physician who matches your needs, we suggest the following:

1. Start with a very broad search, by filling in ONLY the state field.

2. If you live in a very large state, fill in ONLY the zip code field, and check the extended zip code area box. If you need a more refined search, it is ideal to highlight as many of the specialty areas that interest you (press Ctrl button, or the Apple Command button, to highlight more than one specialty).

3. Even if you think you need a specialist, many primary care physicians are adept in treating people with a variety of conditions, so we advise carefully looking over all the physician options in your area.

4. If your search reveals zero results, then no physician in the area that youve specified meets your criteria, and you may need to travel farther to find a Diplomate who meets your needs.

5. Remember: Sometimes, more is not better. If you are not experiencing good results from being specific with specialties and regions, you will have greater success with a broader search.

6. Once you have clicked Search, scroll down the page a bit to reveal the results.

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American Board of Integrative Holistic Medicine Search Doctors

To learn what Integrative Medicine is, listen to Dr. Hernandez by clicking play button below!

What is Integrative Medicine?

At The Center for Health & Integrative Medicine we blend both conventional medicine and natural therapies for optimal health & well-being. Many of our patients come to us because they want a Medical Doctor who also understands and utilizes natural options for health conditions. We believe there are benefits to utilizing a variety of different types of healing modalities. Conventional medicine provides appropriate interventions to deal with acute health challenges, such as heart attacks, broken bones, and traumatic accidents. Prescription medications may also be very useful in these situations. On the other hand, chronic health issues such fatigue, digestive issues, heartburn, and even autoimmune disorders can often be helped by addressing areas such as diet, nutrition, supplementation, and lifestyle. Integrative Medicine looks at the whole person and searches for the root causes of health issues, rather than just treating symptoms. By combining multiple modalities, Integrative Medicine blends the best of both conventional medicine and various natural approaches to create a truly synergistic healing paradigm.

What health conditions may be helped by Integrative Medicine?

Integrative Medicine can be useful in treating a variety of chronic health challenges. Dr. Hernandez has successfully helped many patients with issues such as chronic fatigue, high cholesterol, hormonal imbalances, low thyroid conditions, digestive issues (such as heartburn, irritable bowel syndrome, and chronic constipation), fibromyalgia, low sex drive, diabetes mellitus-type II, and more. In addition to performing conventional medical history and physical examination, Dr. Hernandez has also developed and utilizes a distinctive integrative medical model of analysis, diagnosis, and treatment to assist patients in reclaiming their health, improving quality of life, and enhancing their well-being.

Some of the health conditions treated at The Center for Health & Integrative Medicine include?

Is Dr. Hernandez a Medical Doctor?

Yes. Dr. Hernandez is board certified in Internal Medicine and residency trained in Emergency Medicine. He has over 28 years of clinical experience and has held the position of Medical Director for a multi-physician primary care clinic.

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Integrative Medicine & Functional Medicine - Austin Texas 512 ...

An evolution in medical practice,integrative medicine supports the unique expression of health and vitality for every individual.If you have an interest in learningaboutnon-allopathic techniques, or if you already have training in them, the UMass Worcester Family Medicine Residency is the place to be!

We canhelp you get the training to be effective and supervise your use of these techniques. Whileyou are fine tuning your skills inWestern Medicine, you willgain extensive experience inthe practice of integrativemedicine:

Acupuncture: the ancient practice of using tiny needles to change the energy patterns of the body in order to restore balance and health.

Cupping: used to treat muscular joint pain as well as many systemic diseases. Uses hand-pump or heated cups to create local suction on the skin.

Functional Medicine: addressing the whole person, not just an isolated set of symptoms,practitioners gather extensive personal, medical and social histories. Then, they evaulate the interactions among genetic, environmental and lifestyle factors that can influence long-term health and complex, chronic disease.

GuaSha: also called "coining". Scraping the skin with a blunt tool (coin, spool or other instrument) to treat local pain or systemic problems.

Hypnosis: each day the human mind controls millions of events through the body. Using hypnosis, "inward focus," you can train your mind to influence many areas of function.

Natural Therapies: using non-prescription compounds such as Western or Chinese herbs, or vitamin and mineral supplements to restore balance and function.

Osteopathic Manipulation: OMT can help people of all ages and backgrounds. The treatment can be used to ease pain, promote healing and increase overall mobility .

"After practicing Family Medicine for a few years, I realized that Western medicine had little to offer many patients. I started looking into non-Western therapies and have become an Integrative Medicine Practitioner.Contact me anytime with questions!"Melissa Rathmell, MD, Director of Integrative Medicine UMass Family Medicine ResidencyTo learn more about Dr. Rathmell,we invite you toread our recent interview with her!

American Academy of Medical AcupunctureAmerican Osteopathic AssociationInstitute for Functional MedicineNew England Society of Clinical Hypnosis

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Integrative Medicine - UMass Medical School - Worcester

Integrative Medicine Fellowships

The following is a listing of Fellowships currently approved by the American Board of Integrative Medicine. Completion of one of these fellowship programs satisfies eligibility requirement 7(1). The program listed in red may no longer be open to new applications.

University of Arizona/Arizona Center for Integrative Medicine Fellowship in Integrative Medicine

Bravewell Fellowship Program

University of California Los Angeles Center for East-West Medicine Fellowship in Integrative Medicine

Santa Rosa FamilyMedicineResidency Integrative Family Medicine Fellowship

UCSF Osher Center for Integrative Medicine Training in Research for Integrative Medicine (TRIM)

Scripps Center for Integrative Medicine Integrative Cardiology

Middlesex Hospital Cancer Center Integrative Medicine Fellowship Program

Stamford Hospital, an affiliate of Columbia University Integrative Medicine Fellowship

University of Kansas Integrative Medicine Fellowship

Maine Medical Center Family Medicine Residency Program (MMCFMRP) Integrative Family Medicine (IFM) Program and Fellowship

Harvard Medical School Research Fellowship in Integrative Medicine (multiple locations)

Greater Lawrence Family Health Center HIP Fellowship

University of Michigan Integrative Medicine Fellowship

Mayo Clinic

Albert Einstein College of Medicine/ Beth Israel Medical Center Academic Integrative Medicine Fellowship

Weill Cornell Medical College Fellowship Program in Complementary and Integrative Medicine

University of North Carolina Fellowship in Research in Integrative Medicine

Ohio State University Integrative Medicine Fellowship Program

Academy of Integrative Health & Medicine (AIHM) AIHM Interprofessional Fellowship in Integrative Health & Medicine

Lake Erie College of Osteopathic Medicine Integrative & Lifestyle Medicine Graduate Training Program in Integrative Medicine

Swedish Cherry Hill Integrative Medicine Fellowship

University of Wisconsin, Department of Family Medicine Academic Integrative Medicine Fellowship

The George Washington University Integrative Geriatric Fellowship

The George Washington University Integrative Medicine Fellowship

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Integrative Medicine Fellowships - Medical | Physician

Journal of Pain Research 2015: 8: 437-447

Introduction: This was a prospective case series designed to investigate treatment for anterior cruciate ligament (ACL) tears using an injection of autologous bone marrow concentrate.

Methods: Consecutive adult patients presenting to a private outpatient interventional musculoskeletal and pain practice with knee pain, ACL laxity on exam, and magnetic resonance imaging (MRI) evidence of a grade 1, 2, or 3 ACL tears with less than 1 cm retraction were eligible for this study. Eligible patients were treated with an intraligamentous injection of autologous bone marrow concentrate, using fluoroscopic guidance. Pre- and postprocedural sagittal MRI images of the ACLs were analyzed using ImageJ software to objectively quantify changes between pre- and posttreatment scans. Five different types of measurement of ACL pixel intensity were examined as a proxy for ligament integrity. In addition pain visual analog scale (VAS) and Lower Extremity Functional Scale (LEFS) values were recorded at baseline and at 1 month, 3 months, 6 months, and annually postinjection. Objective outcomes measured were pre- to post-MRI measurement changes, as analyzed by the ImageJ software. Subjective outcomes measured were changes in the VAS and LEFS, and a self-rated percentage improvement.

Results: Seven of ten patients showed improvement in at least four of five objective measures of ACL integrity in their postprocedure MRIs. In the entire study group, the mean gray value, median, raw integrated density, and modal gray value all decreased toward low-signal ACLs (P=0.01, P=0.02, P=0.002, and P=0.08), indications of improved ligament integrity. Seven of ten patients responded to the self-rated metrics follow up. The mean VAS change was a decrease of 1.7 (P=0.25), the mean LEFS change was an increase of 23.3 (P=0.03), and mean reported improvement was 86.7%.

Conclusion: Based on this small case series, autologous bone marrow concentrate shows promise in the treatment of grade 1, 2, and possibly grade 3 ACL tears without retraction. Further investigation using a controlled study design is warranted.

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Orthopedic Stem Cell Research and Related Publications

Also see: Protective Altitude Protect the Mitochondria Lactate Paradox: High Altitude and Exercise Altitude Improves T3 LevelsProtective Carbon Dioxide, Exercise, and PerformanceSynergistic Effect of Creatine and Baking Soda on Performance Altitude Improves T3 Levels Altitude Sickness: Therapeutic Effects of Acetazolamide and Carbon Dioxide Comparison: Carbon Dioxide v. Lactic Acid Carbon Dioxide Basics Universal Principle of Cellular Energy Carbon Dioxide as an Antioxidant Comparison: Oxidative Metabolism v. Glycolytic Metabolic

Over the oxygen supply of the body carbon dioxide spreads its protecting wings. Friedrich Miescher, Swiss physiologist, 1885

===========

People who live at very high altitudes live significantly longer; they have a lower incidence of cancer (Weinberg, et al., 1987) and heart disease (Mortimer, et al., 1977), and other degenerative conditions, than people who live near sea level. As I have written earlier, I think the lower energy transfer from cosmic radiation is likely to be a factor in their longevity, but several kinds of evidence indicate that it is the lower oxygen pressure itself that makes the biggest contribution to their longevity.

The end product of respiration is carbon dioxide, and it is an essential component of the life process. The ability to produce and retain enough carbon dioxide is as important for longevity as the ability to conserve enough heat to allow chemical reactions to occur as needed.

Carbon dioxide protects cells in many ways. By bonding to amino groups, it can inhibit the glycation of proteins during oxidative stress, and it can limit the formation of free radicals in the blood; inhibition of xanthine oxidase is one mechanism (Shibata, et al., 1998). It can reduce inflammation caused by endotoxin/LPS, by lowering the formation of tumor necrosis factor, IL-8 and other promoters of inflammation (Shimotakahara, et al., 2008). It protects mitochondria (Lavani, et al., 2007), maintaining (or even increasing) their ability to respire during stress.

The replicative lifespan of a cell can be shortened by factors like resveratrol or estrogen that interfere with mitochondrial production of carbon dioxide. Both of those chemicals cause skin cells, keratinocytes, to stop dividing, to take up calcium, and to begin producing the horny material keratin, that allows superficial skin cells to form an effective barrier. This process normally occurs as these cells differentiate from the basal (stem) cells and, by multiplying, move farther outward away from the underlying blood vessels that provide the nutrients that are oxidized to form carbon dioxide, and as they get farther from the blood supply, they get closer to the external air, which contains less than 1% as much CO2 as the blood. This normally causes their eventual hardening into the keratin cells, but when conditions are optimal, numerous layers of moist, translucent cells that give the skin the characteristic appearance of youth, will be retained between the basal cells and the condensed surface layers. (Wilke, et al., 1988)

In other types of tissue, a high level of carbon dioxide has a similar stabilizing effect on cells, preserving stem cells, limiting stress and preventing loss of function. In the lining of the mouth, where the oxygen tension is lower, and carbon dioxide higher, the cells dont form as much keratin as the skin cells do. In the uterus, the lining cells would behave similarly, except that estrogen stimulates keratinization. A vitamin A deficiency mimics an estrogen excess, and can cause excessive keratinization of membrane cells.

Certain kinds of behavior, as well as nutrition and other environmental factors, increase the production and retention of carbon dioxide. The normal intrauterine level of carbon dioxide is high, and it can be increased or decreased by changes in the mothers physiology. The effects of carbon dioxide on many biological processes involving methylation and acetylation of the genetic material suggest that the concentration of carbon dioxide during gestation might regulate the degree to which parental imprinting will persist in the developing fetus. There is some evidence of increased demethylation associated with the low level of oxygen in the uterus (Wellman, et al., 2008). A high metabolic rate and production of carbon dioxide would increase the adaptability of the new organism, by decreasing the limiting genetic imprints.

Frogs and toads, being amphibians, are especially dependent on water, and in deserts or areas with a dry season they can survive a prolonged dry period by burrowing into mud or sand. Since they may be buried 10 or 11 inches below the surface, they are rarely found, and so havent been extensively studied. In species that live in the California desert, they have been known to survive 5 years of burial without rainfall, despite a moderately warm average temperature of their surroundings. One of their known adaptations is to produce a high level of urea, allowing them to osmotically absorb and retain water. (Very old people sometimes have extremely high urea and osmotic tension.)

Some laboratory studies show that as a toad burrows into mud, the amount of carbon dioxide in its tissues increases. Their skin normally functions like a lung, exchanging oxygen for carbon dioxide. If the toads nostrils are at the surface of the mud, as dormancy begins its breathing will gradually slow, increasing the carbon dioxide even more. Despite the increasing carbon dioxide, the pH is kept stable by an increase of bicarbonate (Boutilier, et al., 1979). A similar increase of bicarbonate has been observed in hibernating hamsters and doormice.

Thinking about the long dormancy of frogs reminded me of a newspaper story I read in the 1950s. Workers breaking up an old concrete structure found a dormant toad enclosed in the concrete, and it revived soon after being released. The concrete had been poured decades earlier.

Although systematic study of frogs or toads during their natural buried estivation has been very limited, there have been many reports of accidental discoveries that suggest that the dormant state might be extended indefinitely if conditions are favorable. Carbon dioxide has antioxidant effects, and many other stabilizing actions, including protection against hypoxia and the excitatory effects of intracellular calcium and inflammation (Baev, et al., 1978, 1995; Bari, et al., 1996; Brzecka, 2007; Kogan, et al., 1994; Malyshev, et al., 1995).

Bats have a very high metabolic rate, and an extremely long lifespan for an animal of their size. While most animals of their small size live only a few years, many bats live a few decades. Bat caves usually have slightly more carbon dioxide than the outside atmosphere, but they usually contain a large amount of ammonia, and bats maintain a high serum level of carbon dioxide, which protects them from the otherwise toxic effects of the ammonia.

The naked mole rat, another small animal with an extremely long lifespan (in captivity they have lived up to 30 years, 9 or 10 times longer than mice of the same size) has a low basal metabolic rate, but I think measurements made in laboratories might not represent their metabolic rate in their natural habitat. They live in burrows that are kept closed, so the percentage of oxygen is lower than in the outside air, and the percentage of carbon dioxide ranges from 0.2% to 5% (atmospheric CO2 is about 0.038). The temperature and humidity in their burrows can be extremely high, and to be very meaningful their metabolic rate would have to be measured when their body temperature is raised by the heat in the burrow.

Besides living in a closed space with a high carbon dioxide content, mole rats have another similarity to bees. In each colony, there is only one female that reproduces, the queen, and, like a queen bee, she is the largest individual in the colony. In beehives, the workers carefully regulate the carbon dioxide concentration, which varies from about 0.2% to 6%, similar to that of the mole rat colony. A high carbon dioxide content activates the ovaries of a queen bee, increasing her fertility.

Since queen bees and mole rats live in the dark, I think their high carbon dioxide compensates for the lack of light. (Both light and CO2 help to maintain oxidative metabolism and inhibit lactic acid formation.) Mole rats are believed to sleep very little. During the night, normal people tolerate more CO2, and so breathe less, especially near morning, with increased active dreaming sleep.

A mole rat has never been known to develop cancer. Their serum C-reactive protein is extremely low, indicating that they are resistant to inflammation. In humans and other animals that are susceptible to cancer, one of the genes that is likely to be silenced by stress, aging, and methylation is p53, a tumor-suppressor gene.

If the intrauterine experience, with low oxygen and high carbon dioxide, serves to reprogram cells to remove the accumulated effects of age and stress, and so to maximize the developmental potential of the new organism, a life thats lived with nearly those levels of oxygen and carbon dioxide might be able to avoid the progressive silencing of genes and loss of function that cause aging and degenerative diseases.

I think of high altitude as analogous to theprotected gestational state. (Both progesteroneand carbon dioxide are increased in peopleadapted to high altitude.) Respiratory acidosis,meaning the retention of carbon dioxide, is veryprotective, and is an outstanding feature of life inthe uterus. Even at the time that an embryo isimplanting in the uterus, adequate carbon dioxideis crucial. Many of the mysteries of embryologyand developmental biology have been explained by the presence of a high level of carbon dioxideduring gestation. For example, an injury to the fetus heals without scarring, that is, with completeregeneration instead of the formation of a sort ofcollagenous plug. Over the last fifty years, severalpeople have discovered that simply enclosing awound (for example an amputated finger tip) in anair-tight compartment allows remarkably complete regeneration, even in adults, who supposedly have lost the power of regeneration.(Exposure of tissues to air causes them to losecarbon dioxide.)

During gestation, after organs have differentiated,nerve cells extend their fibers from the brain to innervate muscles and other tissues. The specialconditions of life in the uterus support thisprocess, but something similar can happen duringadult life, when damaged nerves regenerate. Amajor difference between injury to the fetus, andinjury to an adult, is that the wound regeneratesperfectly without a scar in the fetus, but in theadult, regeneration is often impaired, and aconnective tissue scar replaces normally functioningtissue.

In childhood, wounds heal quickly, and inflammation is quickly resolved; in extreme old age, or during extreme stress or starvation, wound healing is much slower, and the nature of the inflammation and wound closure is different. In the fetus, healing can be regenerative and scarless, for example allowing a cleft palate to be surgically corrected without scars (Weinzweig, et al., 2002).

The amount of disorganized fibrous material formed in injured tissue is variable, and it depends on the state of the individual, and on the particular situation of the tissue. For example, the membranes lining the mouth, and the bones and bone marrow, and the thymus gland are able to regenerate without scarring. What they have in common with each other is a relatively high ratio of carbon dioxide to oxygen. Salamanders, which are able to regenerate legs, jaw, spinal cord, retina and parts of the brain (Winklemann & Winklemann, 1970), spend most of their time under cover in burrows, which besides preventing drying of their moist skin, keeps the ratio of carbon dioxide to oxygen fairly high.

The regeneration of finger tips, including a well-formed nail if some of the base remained, will occur if the wounded end of the finger is kept enclosed, for example by putting a metal or plastic tube over the finger. The humidity keeps the wound from forming a dry scab, and the cells near the surface will consume oxygen and produce carbon dioxide, keeping the ratio of carbon dioxide to oxygen much higher than in normal uninjured tissue.

Carbon dioxide is being used increasingly to prevent inflammation and edema. For example, it can be used to prevent adhesions during abdominal surgery, and to protect the lungs during mechanical ventilation. It inhibits the formation of inflammatory cytokines and prostaglandins (Peltekova, et al., 2010, Peng, et al., 2009, Persson & van den Linden, 2009), and reduces the leakiness of the intestine (Morisaki, et al., 2009). Some experiments show that as it decreases the production of some inflammatory materials by macrophages (TNF: Lang, et al., 2005), including lactate, it causes macrophages to activate phagocytic neutrophils, and to increase their number and activity (Billert, et al., 2003, Baev & Kuprava, 1997).

Factors that are associated with a decreased level of carbon dioxide, such as excess estrogen and lactate, promote fibrosis. Adaptation to living at high altitude, which is protective against degenerative disease, involves reduced lactate formation, and increased carbon dioxide. It has been suggested that keloid formation (over-growth of scar tissue) is less frequent at high altitudes (Ranganathan, 1961), though this hasnt been carefully studied. Putting an injured arm or leg into a bag of pure carbon dioxide reduces pain and accelerates healing.

In the fetus, especially before the fats from the mothers diet begin to accumulate, signals from injured tissue produce the changes that lead quickly to repair of the damage, but during subsequent life, similar signals produce incomplete repairs, and as they are ineffective they tend to be intensified and repeated, and eventually the faulty repair processes become the main problem. Although this is an ecological problem, it is possible to decrease the damage by avoiding the polyunsaturated fats and the many toxins that synergize with them, while increasing glucose, niacinamide, carbon dioxide, and other factors that support high energy metabolism, including adequate exposure to long wavelength light and avoidance of harmful radiation. As long as the toxic factors are present, increased amounts of protective factors such as progesterone, thyroid, sugar, niacinamide, and carbon dioxide can be used therapeutically and preventively.

For hundreds or thousands of years, the therapeutic value of carbonated mineral springs has been known. The belief that it was the waters lively gas content that made it therapeutic led Joseph Priestley to investigate ways to make artificially carbonated water, and in the process he discovered oxygen. Carbonated water had its medical vogue in the 19th century, but the modern medical establishment has chosen to define itself in a way that glorifies dangerous, powerful treatments, and ridicules natural and mild approaches. The motivation is obviousto maintain a monopoly, there must be some reason to exclude the general public from the practice of medicine. Witch doctors maintained their monopoly by working with frightening ghost-powers, and modern medicine uses its technical mystifications to the same purpose.vAlthough the medical profession hasnt lost its legal monopoly on health care, corporate interests have come to control the way medicine is practiced, and the way research is done in all the fields related to medicine.

I have been using aging (menopause and the ovaries) and cancer (carbon monoxide as a hormone of cellular immortality) to explore the issue of cell renewal and tissue regeneration. Yesterday, Lita Lee sent me an article about K. P. Buteyko, describing his approach to the role of carbon dioxide in physiology and medicine. Buteyko devoted his career to showing that sufficient carbon dioxide is important in preventing an exaggerated and maladaptive stress response. He advocated training in intentional regulation of respiration (avoiding habitual hyperventilation) to improve oxygenation of the tissues by retaining carbon dioxide. He showed that a deficiency of carbon dioxide (such as can be produced by hyperventilation, or by the presence of lactic acid in the blood) decreases cellular energy (as ATP and creatine phosphate) and interferes with the synthesis of proteins (including antibodies) and other cellular materials.

When I first heard of Buteykos ideas, I saw the systemic importance of carbon dioxide, but I wasnt much impressed by his idea of intentionally breathing less. If the hyperventilation is produced by anxiety, then a deliberate focussing on respiration can help to quiet the nerves. Knowing that hyperventilation can make a person faint, because loss of carbon dioxide causes blood vessels in the brain to constrict, I saw that additional carbon dioxide would increase circulation to the brain. This seemed like a neat system for directing the blood supply to the part of the brain that was more active, since that would be the part producing the most carbon dioxide.

In a nutrition class, in the late 70s, I described the way metabolically produced carbon dioxide opens blood vessels in the brain, and mentioned that carbonated water, or soda water, should improve circulation to the brain when the brains production of carbon dioxide wasnt adequate. A week later, a student said she had gone home that night and (interpreting soda water as bicarbonate of soda in water) given her stroke-paralyzed mother a glass of water with a spoonful of baking soda in it. Her mother had been hemiplegic for 6 months following a stroke, but 15 minutes after drinking the bicarbonate, the paralysis lifted, and she remained normal. Later, a man who had stroke-like symptoms when he drank alcohol late at night, found that drinking a glass of carbonated water caused the symptoms to stop within a few minutes.

Realizing that low thyroid people produce little carbon dioxide, it seemed to me that there might be a point at which the circulatory shut-down of unstimulated parts of the brain would become self-sustaining, with less circulation to an area decreasing the CO2 produced in that area, which would cause further vasoconstriction. Carbon dioxide (breathing in a bag, or drinking carbonated water, or bathing in water with baking soda) followed by thyroid supplementation, would be the appropriate therapy for this type of functional ischemia of the brain.

I have been concerned about the probable effects on the fetus of the silly panting respiration that is being taught to so many pregnant women, to use during labor. Panting blows out so much carbon dioxide that it causes vasoconstriction. Possibly the uterus is protected against this, and possibly the fetus produces enough carbon dioxide that it is protected, but this isnt known. Especially if the mother is hypothyroid, it seems that this could interfere with the delivery of oxygen to the fetus. Besides vasoconstriction, Buteyko points out that the Bohr effect, in which CO2 causes hemoglobin to release oxygen, means that a low level of carbon dioxide decreases the availability of oxygen. If the Bohr effect applies to fetal hemoglobin, then this suggests that the mothers panting will deprive the fetal tissues of oxygen.

It is normal for the fetus to be exposed to a high concentration of carbon dioxide. Recent experiments with week-old rats show that carbon dioxide, at the very high concentration of 6% powerfully protects against the brain damage caused by oxygen deprivation (tying a carotid artery and administering 8% oxygen). (R. C. Vannucci, et al., 1995.)

In general, lactic acid in the blood can be takenas a sign of defective respiration, since the breakdownof glucose to lactic acid increases to makeup for deficient oxidative energy production. Normalaging seems to involve a tendency toward excesslactic acid -production, and age-pigment isknown to activate the process. Eliminating respiratorytoxins (such as unsaturated oils, estrogenicand antithyroid substances, lead, and excess iron)is the most obvious first step to take when there isexcess lactic acid formation. Carbon dioxide supplementshave been shown experimentally to reduceresidual lactate production. Many peopleexperience exhilaration when they go to very highaltitudes, and it is known that people generallybum calories faster at high altitude. It has beenfound that, during intense exercise (which alwaysproduces a lactic acid accumulation inthe blood), a lower peak accumulation of lactate occurs at high altitude, and this seems tobe caused by a reduction in the rate of glycolysis,or glucose consumption. (B.Grassi, et aI.)Since there is less oxygen at high elevation, andsince oxygen is used to consume lactic acid, thiseffect is the opposite of what many people expected.In some sense, respiration becomes moreefficient at high altitude. Youth and increased times supported the process by helping to stabilize the high energy metabolism of the brain, and evenby stabilizing the energized state of water thatsupports brain efficiency. Roman Schmitt has proposedthat, 66 million years ago when dinosaursbecame extinct and mammals began their rapidevolution, at that time hydrothermal venting wentwild, releasing huge volumes of carbon dioxideand other substances into the atmosphere.

Antarctic ice cores show there were large increasesin atmospheric carbon dioxide in relativelyrecent times: 10,200, 11,600, and 12,900 yearsago, and two broad peaks in carbon dioxide releaseoccurred just 4,200 and 7,700 years ago(Figge and White.) Local or regional increases incarbon dioxide from volcanism could have morecontinuous effects on brain development.

In times of lower atmospheric carbon dioxide,our Krebs cycle still produces it internally, and therapid development of the brain during gestationtakes advantage of the high concentration of carbon dioxide in the uterus.(These ideas make me doubt the safety of the rapid breathing encouragedby some obstetricians.)

We know that glucose can be metabolized into pyruvic acid, which, in the presence of oxygen, can be metabolized into carbon dioxide. Without oxygen, pyruvic acid can be converted into lactic acid. The production of lactic acid tends to increase the pH inside the cell, and its excretion can lower the pH outside the cell.

The decrease of carbon dioxide that generally accompanies increased lactic acid, corresponds to increased intracellular pH. Carbon dioxide binds to many types of protein, for example by forming carbamino groups, changing the protein conformation, as well as its electrical properties, such as its isoelectric point. With increased pH, cell proteins become more strongly ionized, tending to separate, allowing water to enter the spaces, in the same way a gel swells in an alkaline solution.

The Bohr-Haldane effect describes the fact that hemoglobin releases oxygen in the presence of carbon dioxide, and releases carbon dioxide in the presence of oxygen. When oxygen is too abundant, it makes breathing more difficult, and one of its effects is to cause carbon dioxide to be lost rapidly. At high altitude, more carbon dioxide is retained, and this makes cellular respiration more efficient.

The importance of carbon dioxide to cell control process, and to the structure of the cell and the structure of proteins in general suggested that degenerative diseases would be less common at high altitude. Wounds and broken bones heal faster at high altitude, but the available statistics are especially impressive in two of the major degenerative conditions, cancer and cataracts.

The two biggest studies of altitude and cataracts (involving 12,217 patients in one study, and 30,565 lifelong residents in a national survey in Nepal) showed a negative correlation between altitude and the incidence of cataract. At high altitude, cataracts appeared at a later age. In Nepal, an increase of a few thousand feet in elevation decreased the incidence of cataracts by 2.7 times. At the same time, it was found that exposure to sunlight increased the incidence of cataracts, and since the intensity of ultraviolet radiation is increased with altitude, this makes the decreased incidence of cataracts even more important.

All of the typical causes of cataracts, aging, poisons, and radiation, decrease the formation of carbon dioxide, and tend to increase the formation of lactic acid. Lactic acid excess is typically found in eyes with cataracts.

The electrical charge on the structural proteins will tend to increase in the presence of lactic acid or the deficiency of carbon dioxide, and the increase of charge will tend to increase the absorption of water.

The lens can survive for a considerable length of time in vitro (since it has its own circulatory system), so it has been possible to demonstrate that changes in the composition of the fluid can cause opacities to form, or to disappear.

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Ray Peat, PhD on Carbon Dioxide, Longevity, and ...

The most common vision problems are refractive errors, more commonly known as nearsightedness, farsightedness, astigmatism and presbyopia. Refractive errors occur when the shape of the eye prevents light from focusing directly on the retina. The length of the eyeball (either longer or shorter), changes in the shape of the cornea, or aging of the lens can cause refractive errors. Most people have one or more of theseconditions.

The cornea and lens bend (refract) incoming light rays so they focus precisely on the retina at the back of theeye.

Refraction is the bending of light as it passes through one object to another. Vision occurs when light rays are bent (refracted) as they pass through the cornea and the lens. The light is then focused on the retina. The retina converts the light-rays into messages that are sent through the optic nerve to the brain. The brain interprets these messages into the images wesee.

The most common types of refractive errors are nearsightedness, farsightedness, astigmatism andpresbyopia.

Nearsightedness (also called myopia) is a condition where objects up close appear clearly, while objects far away appear blurry. With nearsightedness, light comes to focus in front of the retina instead of on the retina. Learn more about nearsightedness.

Farsightedness (also called hyperopia) is a common type of refractive error where distant objects may be seen more clearly than objects that are near. However, people experience farsightedness differently. Some people may not notice any problems with their vision, especially when they are young. For people with significant farsightedness, vision can be blurry for objects at any distance, near or far. Learn more about farsightedness.

Astigmatism is a condition in which the eye does not focus light evenly onto the retina, the light-sensitive tissue at the back of the eye. This can cause images to appear blurry and stretched out. Learn more about astigmatism.

Presbyopia is an age-related condition in which the ability to focus up close becomes more difficult. As the eye ages, the lens can no longer change shape enough to allow the eye to focus close objects clearly. Learn more about presbyopia.

Presbyopia affects most adults over age 35. Other refractive errors can affect both children and adults. Individuals that have parents with certain refractive errors may be more likely to get one or more refractiveerrors.

Blurred vision is the most common symptom of refractive errors. Other symptoms mayinclude:

An eye care professional can diagnose refractive errors during a comprehensive dilated eye examination. People with a refractive error often visit their eye care professional with complaints of visual discomfort or blurred vision. However, some people dont know they arent seeing as clearly as theycould.

Refractive errors can be corrected with eyeglasses, contact lenses, orsurgery.

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Common vision problems | National Eye Institute

Biotechnology: One of the Bay Area's Top Growth Industries

The Bay Area is a leader in the global biopharmaceutical industry, with local companies and research institutions setting the pace in the discovery and development of biopharmaceuticals to target major unmet medical conditions, such as cardiovascular disease, cancer, AIDS and other degenerative diseases.

UCSC Extensions Biotechnology Certificate provides a solid understanding of the scientific disciplines that underlie the industrys activities, a foundation in the principles that guide drug discovery and development, an appreciation of cutting-edge bioscience research and technology, and a broader awareness of todays biopharmaceutical industry. This combination of general and practical knowledge enhances the skills of professionals currently working in this industry and helps prepare others to enter this dynamic field.

This program is designed for chemists, biologists and other scientists who want to enhance their knowledge of the principles and applications of biotechnology. It also benefits individuals from other disciplines who need a solid scientific foundation in order to enter or work more effectively in the biopharmaceutical field.

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Biotechnology | UCSC Extension Silicon Valley

Arthritis is very common but is not well understood. Actually, arthritis is not a single disease; it is an informal way of referring to joint pain or joint disease. There are more than 100 differenttypes of arthritis and related conditions. People of all ages, sexes and races can and do have arthritis, and it is the leading cause of disability in America. More than 50million adults and 300,000 children have some type of arthritis. It is most common among women and occurs more frequently as people get older.

Common arthritis jointsymptomsinclude swelling, pain, stiffness and decreased range of motion. Symptoms may come and go. They can be mild, moderate or severe. They may stay about the same for years, but may progress or get worse over time. Severe arthritis can result in chronic pain, inability to do daily activities and make it difficult to walk or climb stairs. Arthritis can cause permanent joint changes. These changes may be visible, such as knobby finger joints, but often the damage can only be seen on X-ray. Some types of arthritis also affect the heart, eyes, lungs, kidneys and skin as well as the joints.

There are different types of arthritis:

Osteoarthritisis the most common type of arthritis. When the cartilage the slick, cushioning surface on the ends of bones wears away, bone rubs against bone, causing pain, swelling and stiffness. Over time, joints can lose strength and pain may become chronic. Risk factors include excess weight, family history, age and previous injury (an anterior cruciate ligament, or ACL, tear, for example).

When the joint symptoms of osteoarthritis are mild or moderate, they can be managed by:

balancing activity with rest

using hot and cold therapies

regular physical activity

maintaining a healthy weight

strengthening the muscles around the joint for added support

using assistive devices

taking over-the-counter (OTC) pain relievers or anti-inflammatory medicines

avoiding excessive repetitive movements

If joint symptoms are severe, causing limited mobility and affecting quality of life, some of the above management strategies may be helpful, but joint replacement may be necessary.

Osteoarthritis can prevented by staying active, maintaining a healthy weight, and avoiding injury and repetitive movements.

A healthy immune system is protective. It generates internal inflammation to get rid of infection and prevent disease. But the immune system can go awry, mistakenly attacking the joints with uncontrolled inflammation, potentially causing joint erosion and may damage internal organs, eyes and other parts of the body. Rheumatoid arthritis and psoriatic arthritis are examples of inflammatory arthritis. Researchers believe that a combination of genetics and environmental factors can trigger autoimmunity. Smoking is an example of an environmental risk factor that can trigger rheumatoid arthritis in people with certain genes.

With autoimmune and inflammatory types of arthritis, early diagnosis and aggressive treatment is critical. Slowing disease activity can help minimize or even prevent permanent joint damage. Remission is the goal and may be achieved through the use of one or more medications known as disease-modifying antirheumatic drugs (DMARDs). The goal of treatment is to reduce pain, improve function, and prevent further joint damage.

A bacterium, virus or fungus can enter the joint and trigger inflammation. Examples of organisms that can infect joints are salmonella and shigella (food poisoning or contamination), chlamydia and gonorrhea (sexually transmitted diseases) and hepatitis C (a blood-to-blood infection, often through shared needles or transfusions). In many cases, timely treatment with antibiotics may clear the joint infection, but sometimes the arthritis becomes chronic.

Uric acid is formed as the body breaks down purines, a substance found in human cells and in many foods. Some people have high levels of uric acid because they naturally produce more than is needed or the body cant get rid of the uric acid quickly enough. In some people the uric acid builds up and forms needle-like crystals in the joint, resulting in sudden spikes of extreme joint pain, or a gout attack. Gout can come and go in episodes or, if uric acid levels arent reduced, it can become chronic, causing ongoing pain and disability.

Diagnosing Arthritis

Arthritis diagnosis often begins with a primary care physician, who performs a physical exam and may do blood tests and imaging scans to help determine the type of arthritis. An arthritis specialist, or rheumatologist, should be involved if the diagnosis is uncertain or if the arthritis may be inflammatory. Rheumatologists typically manage ongoing treatment for inflammatory arthritis, gout and other complicated cases. Orthopaedic surgeons do joint surgery, including joint replacements. When the arthritis affects other body systems or parts, other specialists, such as ophthalmologists, dermatologists or dentists, may also be included in the health care team.

What Can Be Done About Arthritis?

There are many things that can be done to preserve joint function, mobility and quality of life. Learning about the disease and treatment options, making time for physical activity and maintaining a healthy weight are essential. Arthritis is a commonly misunderstood disease. The Arthritis Foundation is the only nonprofit organization dedicated to serving all people with arthritis. Its website, arthritis.org, has many resources for learning about arthritis, practical tips for daily living and more.

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What Is Arthritis?

Conference Series LLCinvites all the participants from all over the world to attend 10th International Conference on Nanomedicine and Nanotechnology in Health Care during July 25-27, 2016 at Avani Atrium, Bangkok, Thailand. It will include presentations and discussions to help attendees address the current trends and research on the applications of Nanomedicine and nanotechnology in healthcare. The theme of the conference is "Embarking Next Generation Delivery Vehicles for affordable Healthcare!"

Nanomedicineis innovating the healthcare industry and impacting our society, but is still in its infancy in clinical performance and applications. The aim of thisNanomedicine 2016conference is to bring together leading academic, clinical and industrial experts to discuss development of innovative cutting-edge Nanomedicine and challenges in Nanomedicine clinical translation.

Track 01:Nanomedicine

Nanomedicine applications in the field of medicine are vast. It helps in the detection, diagnosis, prevention, treatment and follow-up of many diseases.Personalized Nanomedicineis being applied in all the branches of medicine like Radiology, Neurology, Surgery, Pulmonology, Dentistry, Orthopaedics, Ophthalmology etc.Nanomedicine conferencesfocusses on how Nanomedicine can be the next delivery vehicle for making healthcare affordable.

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Nanomaterials Conference April 21-23 2016, UAE; MedicalNanotechnologySummit June 9-11 2016, Dallas; Molecular Nanoscience Meeting September 26-28 2016, UK; Nanotechnology Expo November 10-12 2016, Australia; Nanotech Expo December 5-7 2016, USA; International Conference onNanoscienceand Nanotechnology (ICONN), 711 February 2016, Australia; International Conference onNanobiotechnology, Drug Delivery, and Tissue Engineering, 1st- 2ndApril 2016, Czech Republic; International Conference on Biotechnology, Bioengineering andNanoengineering, April 14-15, 2016, Portugal; Meeting and Expo onNanomaterialsand Nanotechnology, 25th - 27th April 2016, UAE;NANOTEXNOLOGY, 29 July, 2016, Greece, American Society For Nanomedicine, Washington, USA, Society for Personalized Nanomedicine, Florida, USA

Track 02: Nanomedicine and Drug delivery

There are a many ways thatnanotechnologycan make the delivery of drugs more systematic and accost effective treatment for the patient. Numerous biological materials like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles are under investigation for preparation of nanoparticles. The hazards that are introduced by usingnanoparticles for drug deliveryare more than that posed by conventional hazards imposed by chemical delivery.

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Bioavailability and Bioequivalence Summit August 29-31, 2016, USA;Surgical OncologyConference during September 01-03, 2016, Brazil; Precision Medicine ConferenceNovember 03-05, 2016, USA; Translational MedicineConference November 17-19, 2016, USA;Mesothelioma Summit,November 03-04, 2016, Spain; International Conference onBiotechnologyand Nanotechnology, April 14-15, 2016, Portugal;Nanotech Conference & Exhibition, 01-03 June, 2016, France; Materials Scienceand Nanotechnology Conference July 28- 29, 2016, China; 7thInternationalnanotechnology Summit: fundamentals and applications, August 19-10, 2016 Hungary, Society for Personalized Nanomedicine, Florida, USA, European Society for Nanomedicine, Basel, Switzerland

Track 03:Nanomedicine and Nanotechnology

Nanomedicine is an emerging specialty born from Nanotechnology. Bothnanomedicine and nanotechnologyare emerging as the new direction in the diagnosis and drug therapy. Nanomedicine can change the face of healthcare in the future using nanotechnology.Nanomedicinehelps detect, repair, understand and control the human biological system. Nanomedicine can be used forpersonalized Nanomedicine.

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Nanomaterials Conference April 21-23 2016, UAE; MedicalNanotechnologySummit June 9-11 2016, Dallas; Molecular Nanoscience Meeting September 26-28 2016, UK; Nanotechnology Expo November 10-12 2016, Australia; Nanotech Expo December 5-7 2016, USA; International Conference onNanoscienceand Nanotechnology (ICONN), 711 February 2016, Australia; International Conference onNanobiotechnology, Drug Delivery, and Tissue Engineering, 1st- 2ndApril 2016, Czech Republic, Biotechnology, Bioengineering andNanoengineering Conference, April 14-15, 2016, Portugal; Nanomaterials Conferenceand Nanotechnology, 25th - 27th April 2016, UAE;NANOTEXNOLOGY, 29 July, 2016, Greece, International Association of Nanotechnology, California, USA, French Society for Nanomedicine, Lille, France

Track 04:Nanomedicine and Nanobiotechnology

Nanobiotechnologyis the intersection of nanotechnology and biology. Nanobiotechnology has multitude of potentials for advancing medical science thereby improving health care practices around the world. Nanomedicine is used to treat diseases bygene therapy. Nano biotechnologies are being applied to molecular diagnostics and several technologies are in development.

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NanoConference June 20-21, 2016 Cape Town, South Africa; Medical NanotechnologyCongress and Expo June 9-11, 2016 Dallas, USA; Nanotechnology Congress June 27-29, 2016 Valencia, Spain; 11th Nanobiotechnology MeetingSeptember 26-28, 2016 London, UK: Nanotechnology Expo November 10-12, 2016 Melbourne, Australia: International Conference on NanotechnologyModellingand Simulation April 1-2, 2016 Prague, Czech Republic: The 5th Conference onNanomaterialsJanuary 14-16, 2016 Bangkok, Thailand: Nanotechnology Conference and Expo Baltimore, USA, 4th to 6th April 2016: 4thNanoscience Conference (ICNT2016) Kuala Lumpur, Malaysia, 28th - 29th January 2016: 4th Conference on Materials ScienceNew York, USA, American Nano Society, Florida, USA, Sustainable Nanotechnology Organization, Washington, USA

Track 05:Nanomedicine and Bioengineering

Nanomedicinehas a considerable role in Bioengineering. To design and construct an apt scaffold is the major challenge inRegenerative medicinetoday. The cell-cell and cell-matrix interactions in the biosystems happen at the nanoscale level. Therefore the application of nanotechnology at that level helps in modifying the cellular function to mimic the native tissue in a more appropriate way. The application ofBioengineeringhas transformed the designing the manufacturing of scaffolds and artificial grafts.

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Stem Cell Research conference February 29-March 02 2016, USA, Bio banking ConferenceAugust 18-19 2016, USA; Regenerative Medicine Conference,September 12-14 2016, Germany; 6th Pharmacogenomics ConferenceSeptember 12-14, 2016, Berlin, Germany; Conference onRestorative MedicineOctober 24-26, 2016, USA ; Conference onRegeneration, January 10 14, 2016, USA; ISSCR Conference onNeural Degenerationand Disease, 18th Biotechnology Meeting, April 11-12, 2016, Italy; 14th European Symposium on Drug Delivery, 13th-15thApril 2016, The Netherlands Sustainable Nanotechnology Organization, Washington, USA, Asian Nanoscience and Nanotechnology Association, Kagawa, Japan

Track 06:Nanomedicine and Cancer

Cancer Nanomedicineaims to use the nanostructures and nanoscale processes for the prevention, detection, diagnosis and treatment of cancer and other concomitant areas. Even when molecular changes occur in a smaller percentage of cells, which may be cancer related targets.Nanomedicine in cancercan help in the sensitive detection of them. The use of Nanotechnology to combat cancer is still under development. Severalnanocarrierdrugs andnanotherapeuticsare available in market and some in Clinical trials.

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CancerDiagnostics Expo June 13-15 2016, Italy; Conference onCancer Immunologyand Immunotherapy July 28-30 2016, Australia;Cancer GenomicsSummit August 8-9 2016, USA; 12th Cancer TherapySummit September 26-28 2016, UK; International Conference onCervical CancerSeptember 22-23 2016, Austria; TheBiomarkerConference, 18th-19th February 2016, USA; Cancer Vaccines: Targeting Cancer Genes forImmunotherapy, March 610 2016, Canada; 18th Conference on Biotechnology Advances, April 11-12, 2016, Italy; 14th European Drug Delivery Summit, April 13-15 2016, The Netherlands; 18th InternationalCancer NanomedicineConference and Novel Drug Delivery Systems, April 22 - 23, 2016, United Kingdom, Asian Nanoscience and Nanotechnology Association, Kagawa, Japan, European Nanoscience and Nanotechnology Association, Bulgaria.

Track 07:Nanomedicine and Healthcare

Nanomedicineaffects almost all the aspects of healthcare. Nanomedicine helps to engineer novel and advanced tools for the treatment of various diseases and the improvement of human biosystems usingmolecular Nanotechnology. Cardiovascular diseases, Neurodegenerative disorders, Cancer, Diabetes, Infectious diseases, HIV/AIDS are the main diseases whose treatment can be benefitted by using nanomedicine.

RelatedNanomedicine Conferences|Nano science Meeting |Healthcare Meeting:

Bioequivalence and Bioavailability Summit August 29-31, 2016, USA;Surgical OncologyConference during September 01-03, 2016, Brazil; Precision Medicine ConferenceNovember 03-05, 2016, USA; Translational MedicineConference November 17-19, 2016, USA;Mesothelioma Summit,November 03-04, 2016, Spain; International Conference onBiotechnologyand Nanotechnology, April 14-15, 2016, Portugal;Nanotech Conference & Exhibition, 01-03 June, 2016, France; Materials Scienceand Nanotechnology Conference July 28- 29, 2016, China; 7thInternationalnanotechnology Summit: fundamentals and applications, August 19-10, 2016 Hungary, Society for Personalized Nanomedicine, Florida, USA, European Society for Nanomedicine, Basel, Switzerland

Track 08:Nanomedicine and Healthcare Applications

Nanomedicineapplications in healthcare Industry are broad. It helps to engineer newNano medical devices, design nanoparticles for detection and drug delivery in cancer. Nanomedicine can be applied in allied areas of healthcare like Wound healing, Food Industry and Hair growth. Nanomedicine is being widely used forpublic health and Nutrition.

RelatedNanomedicine Conferences|Nanotechnology Conferences|Healthcare Meeting:

NanoConference June 20-21, 2016 Cape Town, South Africa; Medical NanotechnologyCongress and Expo June 9-11, 2016 Dallas, USA; Nanotechnology Congress June 27-29, 2016 Valencia, Spain; 11th Nanobiotechnology MeetingSeptember 26-28, 2016 London, UK: Nanotechnology Expo November 10-12, 2016 Melbourne, Australia; International Conference on NanotechnologyModellingand Simulation April 1-2, 2016 Prague, Czech Republic: The 5th Conference onNanomaterialsJanuary 14-16, 2016 Bangkok, Thailand: Nanotechnology Conference and Expo Baltimore, USA, 4th to 6th April 2016: 4thNanoscience Conference (ICNT2016) Kuala Lumpur, Malaysia, 28th - 29th January 2016: 4th Conference on Materials ScienceNew York, USA, American Nano Society, Florida, USA, Sustainable Nanotechnology Organization, Washington, USA.

Track 09: Nanotechnology and Food

Nanotechnology has begun to find potential applications in the area of functional food by engineering biological molecules toward functions very different from those they have in nature, opening up a whole new area of research and development. Of course, there seems to be no limit to whatfood technologistsare prepared to do to our food and nanotechnology will give them a whole new set of tools to go to new extremes. Nanotechnology may revolutionize the food industry by providing stronger, high-barrier packaging materials, more potent antimicrobial agents, and a host of sensors which can detect trace contaminants, gasses or microbes in packaged foods.

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Biopolymers Congress, August 01-03, 2016, UK; Conference onSustainable BioplasticsNovember 10-12, 2016, Spain; Biopolymers andBioplastics Summit, September 12-14, 2016, USA; Biofuelsand Bioenergy September 1-3, 2016, Brazil; Public HealthSummit March 10-12, 2016, Spain; 5th Annual PharmaceuticalMicrobiology Conference, 2021 January 2016, United Kingdom; 18th International Conference on Biomaterials,Colloidsand Nanomedicine, January 21-22, 2016, France; 13th National Conference and Technology Exhibition On Medical Devices &PlasticsDisposables, February 12-13, 2016, USA; 18th International Conference onToxicology, February 25 - 26, 2016; United Kingdom; Faraday Discussion:Nanoparticleswith Morphological and Functional Anisotropy, 46 July 2016, United Kingdom, Asian Nanoscience and Nanotechnology Association, Kagawa, Japan, European Nanoscience and Nanotechnology Association, Bulgaria

Track 10:Nanomedicine and Nanotheranostics

Nanotheranosticscombine both the Non-invasive diagnosis and treatment of diseases and helps to monitor the drug release and dispersion of the drug, thereby increasing the effectiveness of therapy.Cancer nanotheranosticshold a great promise in improving the treatment outcomes in Cancer. Nanotheranostics are currently being used in theBiomarker Discovery. Nanotheranostics include both Genomics based theranostics and Proteomics based theranostics

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Track 11: Nanomedicine and Nanobiology

Nano biologyis the branch where basic biology of the organism and nanotechnology meet. Nano biology helps in addressing the basic mechanisms of human health and diseases at the cellular and molecular level.Nano biologyapplied in microbiology is Nanomicrobiology. Recently certain nanoparticles are being designed to act against infections

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Track 12:Nanomedicine and Nanopharmaceuticals

Nanopharmaceuticalssuch as liposomes,quantum dots, dendrimers,carbon nanotubesand polymeric nanoparticles have brought considerable changes in drug delivery and the medical system. Nanopharmaceuticals offer a great benefit for the patients in comparison with the conventional drugs. There are several advantages of these drugs such as enhanced oral bioavailability, improved dose proportionality, enhanced solubility and dissolution rate, suitability for administration and reduced food effects.

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Track 13:Nanomedicine and Nanotoxicology

Nanotoxicologyis intended to address the toxicological activities of nanoparticles and their products to determine whether and what extent they may pose a threat to the environment and to human health and defined as the study of the nature and mechanism of toxic effects of nanoscale materials/particles on living organisms and other biological systems. It also deals with the quantitative assessment of the severity and frequency of nanotoxic effects in relation to the exposure of the organisms. The knowledge from nanotoxicology study will be the base for designing safenanomaterialsandnanoproducts,and also direct used innanomedicalsciences.

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Track 14:Nanomedicine and Nanomedical Devices

Nanomedical devicesshow great promise in various applications for health care. Many nano scale devices have already been approved by the FDA. Nano scale materials can be used as delivery mechanisms allowing cells to absorb therapeutics into the cell wall. Various nano materials are being researched for use in cancer therapeutics.Nanowiresand needles are being researched and developed for use in epilepsy and heart control.Nanosized surgical instrumentscan be used to perform microsurgeriesand better visualization of surgery.

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Track 15:Nanomedicine and Nanodiagnostics

The use of Nanotechnology in clinical diagnosis is termed asNano diagnostics. Diagnosis at the single cell level or molecular level can be possible through Nano diagnostics. They can even be incorporated even in the current diagnostic methods like Biochips.Nanobiosensorsare promising devices for Clinical applications.

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Track 15:Nanoethics and Regulations

Nanoethicsis the study ethical and social implications of nanotechnologys. It is an emerging but controversial field.Nanoethics is a debatable field.As the research is increasing on nanomedicine, there are certain regulations to increase their efficacy and address the associated safety issues. Other issues in nanoethics include areas likeresearch ethics, environment,global equity, economics, politics, national security, education, life extension and space exploration.

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Track 17:Nanomedicine Technologies

Nanomedicine technologiescould find an enhanced position in various areas and applications of the healthcare sector including drug delivery, drug discovery, screening and development, diagnostics and medical devices.BIOMEMSrefers to the application of micro electromechanical systems to micro- and nanosystems for genomics, proteomics, drug-delivery analysis, molecular assembly, tissue engineering, biosensor development, nanoscale imaging, etc.Nanoroboticsrefers to the still largely theoretical nanotechnology engineering discipline of designing and building nanorobots. Different companies are developing novel technologies in Nanomedicine likeNanoTherm therapyandNanobody technology. Nanomedicine in drug discovery is playing a key role in the growing part of pharmaceutical research and development.

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Conference Series LLCinvites the contributors across the globe to participate in the premier International Conference on Nanomedicine and Nanotechnology in Health Care (Nanomedicine-2016), to discuss the theme: "Nanomedicine: The Remarkable Technology Thats Changing the Face of Healthcare The conference will be held at Avani Atrium, Bangkok, Thailand during July 25-27,2016.

Conference Series Llc organizes a conference series of 1000+ Global Events inclusive of 300+ Conferences, 500+ Upcoming and Previous Symposiums and Workshops in USA, Europe & Asia with support from 1000 more scientific societies and publishes 700+ Open access journals which contains over 30000 eminent personalities, reputed scientists as editorial board members

International Conference on Nanomedicine and Nanotechnology in Health Care (Nanomedicine 2016) aims to bring together leading academic scientists, researchers and research scholars to exchange and share their experiences and research results about all aspects of Nanomedicine in Healthcare. It also provides the premier interdisciplinary forum for researchers, practitioners and educators to present and discuss the most recent innovations, trends, and concerns, practical challenges encountered and the solutions adopted in the field of Nanomedicine. The conference program will cover a wide variety of topics relevant to the nanomedicine, including: nanomedicine in drug discover and delivery, nanodiagnostics, theranostics, applications of nanomedine in healthcare applications and disease treatments.

Why to attend?

With members from around the world focused on learning about nanomedicine and its advances; this is your best opportunity to reach the largest assemblage of participants from the Nanotechnology community. Conduct presentations, distribute information, meet with current and potential scientists, make a splash with new drug developments, and receive name recognition at this 3-day event.

Target Audience:

Nanomedicine Academia Professors , Medical professionals, Nanomedicine Department heads, Nanomedicine researchers, Nanomedicine CTOs, Nanomedicine product managers, business development managers, Entrepreneurs, Industry analysts, Investors, Students, Media representatives and decision makers from all corners of Nanoscience research area around the globe.

We therefore encourage all colleagues from all over the world to participate and help us to make this an unforgettable important and enjoyable meeting.

We look forward to seeing you in Bangkok, Thailand !!!

For more

10th International conference on Nanomedince and Nantotechnology in Healthcare

July 25-27, 2016 Bangkok, Thailand

Summary of Nanomedicine Conference:

Nanomedicine 2016 welcomes attendees, presenters, and exhibitors from all over the world to Bangkok, Thailand. We are delighted to invite you all to attend and register for the 10th International conference and exhibition on Nanomedicine and Nanotechnology in Healthcare which is going to be held during July 25-27, 2016 at Bangkok, Thailand. The organizing committee is gearing up for an exciting and informative conference program including plenary lectures, symposia, workshops on a variety of topics, poster presentations and various programs for participants from all over the world. We invite you to join us at the Nanomedicine-2016, where you will be sure to have a meaningful experience with scholars from around the world. All the members of Nanomedicine 2016 organizing committee look forward to meet in person.

Scope and Importance:

The emergence of nanomedicine and the application of nanomaterials in the healthcare industry will bring about groundbreaking improvements to the current therapeutic and diagnostic scenario. Some of the drivers of this market include increasing research funding, rising government support, improved regulatory framework, technological know-how and rising prevalence of chronic diseases such as diabetes, cancers, obesity, kidney disorders, orthopedic diseases and others.

Market Analysis:

In the past few years, the global nanomedicine market has witnessed an increasing use of novel nanomaterials and emergence of nanorobotics on a global front. The market has also observed a significant demand for personalized medicines due to its ability to treat patients based on customized treatments and other medical and genetic conditions.

Overall research in various disciplines:

The North American nanomedicine market held the majority of global market share in 2012 because of the rapidly growing nanomedicine market in the Asia-Pacific, Latin American and African region, presence of large number of patented nanomedicine products and favorable regulatory framework in the region. In addition, the presence of sophisticated healthcare infrastructure supports development of advanced products such as nano probes, nanorobots, monoclonal antibody based immunoassays and nanoparticle based imaging agents for early detection of diseases.

However, the Asia-Pacific region is expected to grow at a faster CAGR owing to presence of high unmet healthcare needs, research collaborations and increase in nanomedicine research funding in emerging economies such as China, India and other economies in the region. China is expected to surpass the United States in terms of nanotechnology funding in the near future, which indicates the growth offered by this region.

Nanomedicine study in various countries:

Companies involved in Nanomedicine:

GE Healthcare, Mallinckrodt plc, Nanosphere Inc., Pfizer Inc., Merck & Co Inc., Celgene Corporation, CombiMatrix Corporation, Abbott Laboratories are some of the major companies in the Nanomedicine market.

Why Bangkok, Thailand?

Bangkok is the cultural, economic and political capital of Thailand. The city features both old-world charm and modern convenience. Many visitors in Bangkok are overwhelmed by the sheer size of the city and the vast number of attractions it has to offer. Indeed, there are many sightseeing opportunities in Bangkok, spanning for more than two centuries of rapid development following the citys founding in 1782. As Bangkok is considered a transport hub and a popular travel destination in Asia, we believe it would be beneficial to all the delegates who are attending the conference.

At present the research on nanomedicine is currently less due to the unavailability of funds and lack of proper expertise. The Asia-Pacific region is expected to grow at a faster CAGR owing to presence of high unmet healthcare needs, research collaborations and increase in nanomedicine research funding in emerging economies such as China, India and other economies in the region. China is expected to surpass the United States.

Conference Highlights:

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Healthy aging and longevity in humans are modulated by a lucky combination of genetic and non-genetic factors. Family studies demonstrated that about 25% of the variation in human longevity is due to genetic factors. The search for genetic and molecular basis of aging has led to the identification of genes correlated with the maintenance of the cell and of its basic metabolism as the main genetic factors affecting the individual variation of the aging phenotype. In addition, studies on calorie restriction and on the variability of genes associated with nutrient-sensing signaling, have shown that ipocaloric diet and/or a genetically efficient metabolism of nutrients, can modulate lifespan by promoting an efficient maintenance of the cell and of the organism. Recently, epigenetic studies have shown that epigenetic modifications, modulated by both genetic background and lifestyle, are very sensitive to the aging process and can either be a biomarker of the quality of aging or influence the rate and the quality of aging.

On the whole, current studies are showing that interventions modulating the interaction between genetic background and environment is essential to determine the individual chance to attain longevity.

The research on aging, and in particular the search for the determinants of successful aging and longevity, has been continuously growing in the last decades also due to the social and medical burden correlated to the continuous increase of lifespan in western countries and the consequent grow of the elderly population. One of the main questions in this field is the correlation between the genetic background and lifestyle in determining the individual chance of a delayed aging (possibly without age-related diseases and disabilities) and longevity. The results obtained by biogerontologists in these years, which highlighted most of the biological and biochemical mechanisms involved in the aging process, allowed to better understand such correlation. This has brought to elaborate important strategies focused on possible interventions to improve lifestyle in order to increase the chance to attain longevity by modulating the basic molecular mechanisms of aging.

Before the 1990ies it was largely spread the idea that aging is ineluctable and that genetics does not control it. It was important, in this view, the idea that aging occurs after reproduction, and then there is no need, but also no opportunity, for selection to act on genes that are expressed during this late period of life [1].

The researcher who pioneered the genetics of aging and longevity was Tom Johnson, who studied groups of C. elegans where he was able to separate long living individuals from short living subjects. The analysis of hybrids obtained from different strains of C. elegans, allowed to estimate that the heritability of life-span was between 20 and 50% [2, 3]. Subsequently, he started the analysis of different mutants and, with M. Klass, found a number of mutants with longer lifespan. Subsequently, Tom Johnson found out that most of the mutants with long lifespan had mutations in the age1 gene [4]. This gene turned out to be the catalytic subunit of class-I phosphatidylinositol 3-kinase (PI3K).

The studies of Johnson clearly demonstrated that genetic variability could indeed affect lifespan. This triggered many studies in model organisms in order to disentangle the different biochemical pathways which could affect lifespan, and to highlight the genes coding for the proteins involved in such pathways. In particular, yeast, C. elegans, drosophila and mice were analyzed and this highlighted numerous genes which could affect lifespan if mutated (for an updated list of these genes see http://genomics.senescence.info/genes/models.html). Most of these genes are related to the maintenance of the integrity of the cell (especially the integrity of DNA). In C. elegans, however, some of the main genes which have been found to modulate lifespan (daf2, daf16) are related to the ability to enter the dauer status [5, 6], that is a quiescent status (usually entered in case of nutrient deprivation) with a minimum energy expense, which causes an arrest of the reproduction process and allows the organism to live longer expecting for the availability of nutrients. This suggested that longevity can be attained by means of an efficient maintenance of the cell but also by diverting resources from reproduction to self maintenance, in line with previous findings that dietary restriction can extend lifespan. After the characterization of these genes in C. elegans, it was found that in mice the ortholog of daf16 (FOXO) could affect lifespan. In mammals, FOXO is correlated to the Insulin/IGF1 axis which is stimulated by nutrient availability and, through FOXO, promotes protein synthesis [711].

It is of note that some Authors suggested these molecular mechanisms modulating lifespan could be due to a pleiotropic effect of genes which have evolved for different purposes (such as the genes in the IGF-1 pathway which have evolved to face presence/absence of nutrients) but can, ultimately affect lifespan; others proposed that some genes may have evolved to program aging and avoid immortality, as this would hamper the continuous substitution of old subjects with new, younger, ones [12, 13].

It was obviously inevitable that the research of the genetic basis of longevity turned to human beings and investigated whether the common genetic variability of human populations could affect inter individual differences in lifespan but also whether the genes found to prolong lifespan in model organisms, on turn, were correlated to human lifespan.

As to the first question (does common genetic variability affect lifespan, and in particular does it affect longevity?), this has been studied by two approaches. The first one was the reconstruction of the sibships of long-lived subjects [14, 15] and the comparison of their survival curves with those of the birth cohorts born in the same geographical area. This approach demonstrated that brothers and sisters of the long-lived subjects had a clear survival advantage (at any age) with respect to the general population. The second approach, with intrafamily controls, was started in order to distinguish the genetic from the familiar effect. Montesanto et al. [15] compared the survival function of brothers of centenarians with those estimated for their brothers in law, that is with the men who married their sisters; these men were supposed to share with the brothers of the long lived subjects the familiar environment. By using this second approach, it has been found that the survival advantage of siblings of long-lived subjects was not completely shared by their brothers in law, despite they shared the same environment for most of their life. This suggested that beyond the family environment, there are genetic factors influencing survival and, consequently, lifespan. Interestingly, in this study, the survival curve of the sisters of long-lived subjects did not differ from the one of sisters in law, suggesting that the genetic component does explain lifespan in men more than in women. The genetic component of lifespan in humans has also been analyzed by comparing the age of death of monozygotic and dizygotic twins. This has allowed to estimate that about 25% of the variation in human longevity can be due to genetic factors and indicated that this component is higher at older ages and is more important in males than in females [1618].

In parallel to these studies, many researches have been carried out to search the genetic variants responsible of modulating human longevity. Most of them were carried out by a case/control approach, by comparing the frequency of specific polymorphisms in long-lived subjects and in younger geographically matched controls. The rationale of this study design is that as the population ages, alleles favorable for survival will be present at higher frequency among long-living people, while unfavorable alleles will be eliminated [1921]. The candidate genes analyzed by this approach were either genes involved in age-related diseases (such as APOE, which had been observed to be involved in the predisposition to Alzheimer Disease and other age-related cognitive impairments), or genes implicated in pathways related to longevity in studies with model organisms (IGF-1, FOXO, Sirtuins) [2225]. This study design has indeed led to find numerous polymorphic genes the variability of which affects longevity. However, each of these polymorphisms turned out to explain only a very small fraction of the longevity variability. Indeed high-throughput Genome-wide analyses, which have recently been carried out have identified many genes positively associated with longevity but only a very few ones could hold multiple test significance and successfully replicated in different studies and across different populations [2629]. Population stratification and inadequate sample sizes are among the main plausible explanations [30]. The adoption of innovative study design and the development of new statistical and computational tools for effective processing of genetic data arising from high-throughput DNA technologies will help to better understand the complex genetic architecture underlying human longevity [31, 32].

A new way of looking at the genetic data has been proposed by Raule et al. [33] who analyzed the complete sequences of mitochondrial DNA from long-lived subjects coming from different areas of Europe. The availability of complete sequences allowed to evaluate for the first time the cumulative effects of specific, concomitant mitochondrial DNA (mtDNA) mutations, including those that per se have a low, or very low, impact. The analysis indicated that the presence of single mutations on mtDNA complex I may be beneficial for longevity, while the co-occurrence of mutations on both complexes I and III or on both I and V might lower the individuals chances for longevity. Previous analyses on single mutations falling on complex I (either specific mutations or mutations defining groups of haplotypes) had given contrasting results, showing association with longevity in some cases but not in others. It is likely that positive results were obtained in populations were mutations on complex I were not associated with mutations on complex III or V, while negative results were obtained in populations with high prevalence of mtDNA haplotypes carrying mutations on complex I in association with mutations in complex III and V. This approach confirmed that most of the genetic variants have a very limited effect on longevity, and that only their cumulative effect can give a consistent appreciable effect and suggests that a limit of previous analyses has been to search for single mutations instead of cumulative effects. On the other hand, it is very difficult to think of using such approach, which has been successful for mitochondrial DNA, on genomic DNA unless small fractions (or specific regions harboring genes involved in relevant pathways) are analyzed.

On the whole, the genetic association studies suggested that, also in humans, mutations in genes correlated with the maintenance of the cell and of its basic metabolism are essential in modulating lifespan. Indeed, genes involved in DNA repair [34], telomere conservation [3537], heat shock response [38, 39], and the management of free radicals levels [33, 40] were found to contribute to longevity or, in case of reduced functionality, to accelerated senescence (cellular aging) and the consequent organism aging. In addition, as suggested by the studies in mice, the pathways involved in nutrient-sensing signaling and in regulating transcription, such as IGF-1/insulin axis [41] and TOR (target of rapamycin) [42] showed to be involved in modulating human longevity. Besides these genes involved in cellular maintenance/metabolism and senescence, concurrent efforts, especially from clinical studies, also showed that genes implicated in important organismal process may have a strong impact on aging and longevity. For instance genes involved in lipoprotein metabolism (especially APOE), cardiovascular homeostasis, immunity, and inflammation have been found to play an important role in aging, age-related disorders, and organism longevity [4346].

Life expectancy at birth has been increasing for most of the last century in western societies, thanks to the continuous amelioration of medical assistance, to the improvement of the environment (in particular clean, safe water and food), and to the improvement of nutrients. For instance, in Italy life expectancy went from 29years in 1861 to 82 in 2011 (Table

reports the evolution of this data in women and men). Similarly, the extreme longevity has been growing in these years. Indeed, the number of centenarians (still in Italy) remarkably increased from 165 in 1951 to more than 15000 in 2011. These results have been attained first by a dramatic reduction of infectious diseases, which, on turn, has dramatically reduced infantile mortality, but also mortality in adult age. In fact, in 2011 less than 10% of deaths occurred in subjects under 60years of age, while the corresponding figures were 74% in 1872, 56% in 1901 and 25% in 1951. However, in the last decades, the continuous extension of lifespan was mainly due to the improvement of medical assistance with respect to age-related diseases, especially Cardiovascular Diseases and Cancer, which allowed to increase lifespan of 5years in the last 2 decades and of 2years in the last 10years (data from

and

).

Evolution of lifespan expectancy in Italy from 1861

1861

28

29

29

1871

30

31

30

1881

35

35

35

1891

38

39

38

1901

43

43

43

1911

46

46

46

1921

48

50

49

1931

53

56

55

1941

55

58

56

1951

63

67

65

1961

67

72

69

1971

69

75

72

1981

71

78

75

1991

74

80

77

2001

77

83

80

2011

79

84

82

These data clearly show that environmental factors have a very strong impact on lifespan and on longevity in humans. However, the extension of lifespan that there has been in the last decades have not been accompanied by a similar extension of healthy lifespan. Indeed, in most cases this lifespan extension is due to the chronicit of the age-related diseases. This has brought the community of biogerontologists to study interventions, possibly modulated on the knowledge emerged from the studies on the genetic and biomolecular basis of longevity, to extend not only lifespan but also healthy lifespan, or, with a new word, healthspan. In fact, model organisms with mutations that extend lifespan have a healthy life also when they are old. This suggested that health span extension could be attained by targeting (stimulating or silencing) the genes, which had been highlighted to be involved in life extension in both model organisms and humans [47]. In support of this hypothesis, it has been reported that dietary restricted mice, which live much longer and show a very delayed aging phenotype than mice fed at libitum, at old age have an expression pattern very different from mice of the same age for a number of genes correlated with life extension, such as those related to DNA repair, stress response, immune response and others [48, 49]. Thus, dietary restriction can trigger a molecular-genetic response which postpones aging and age-related phenotypes. This has brought to search for drugs or interventions which may act on these mechanisms without the side effects of calorie restriction. Among the most important interventions which have been considered in this context, we may name the protein restriction, the use of drugs targeting different genes of IGF-1 axis or of the FOXO/TOR pathway [47]. In addition, these studies have allowed to reconsider previous data on some areas characterized by exceptional longevity (such as Okinawa, Sardinia and Calabria) which are characterized by traditional ipoproteic diets, such as the Mediterranean diet [5053]. In these cases, then, the environment, that is the traditional diet, has allowed to stimulate the molecular mechanisms which can increase life span.

Among the several changes that occur with the aging process, in the last decade Epigenomics has attracted the interest of many researchers. This was mainly due to the fact that epigenetic modifications summarizing, at least in part, the interaction between the individual genetic background and lifestyle characteristics, should be potentially able to capture part of the unexplained susceptibility observed today for complex diseases (the so-called missing heritability problem).

Starting from the pioneeristic observations that epigenetic modifications affect not only the aging process but also its quality (successful aging) [54], EpiGenome-Wide Association Studies identified hundreds of sites spread along the entire genome in which methylation levels change between oldest old and younger subjects. In particular, Horwat and co-workers, on the basis of the methylation levels of 353 CpG units, formulated a mathematical model, the so-called epigenetic clock, that showed some important properties [55]. First, it was able predict the chronological age of a subject starting from the methylation level of several cells and tissues of his body. Second, it represents one of the most accurate biomarker of age (also superior to the estimates obtained from the telomere length). Third, using methylation levels of blood and brain tissues from subjects affected by Down syndrome, it showed that an accelerated aging occur in such a syndrome [56]. Fourth, it was able to predict all-cause mortality also after adjusting for traditional risk factors [57]. Finally, when it was used to estimate the biological age of several tissues from supercentenarians, it has been demonstrated that brain and muscle represent the youngest tissues of these exceptional individuals [58].

However, even if the cause-effect relationship between methylation process and aging is still not clear, the potential applications of this discovery are very wide, ranging from detailed monitoring of changes occurring with age within individual systems or organs (muscle, brain, etc.) to forensic purposes. For this and several other reasons, future advances in this field could help the understanding of the complex physiology of aging, lifespan and age-associated diseases.

See the article here:
Human longevity: Genetics or Lifestyle? It takes two to ...

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