Dr Bryant Villeponteau the formulator of Stem Cell 100 and other Life Code nutraceuticals was recently interviewed by Dr Mercola who owns the largest health web site on the internet. Dr. Villeponteau is also the author of Decoding Longevity an new book which will be released during December. He is a leading researcher in novel anti-aging therapies involving stem cells an area in which he has been a pioneer for over three decades.

Stem cell technology could have a dramatic influence on our ability to live longer and replace some of our failing parts, which is the inevitable result of the aging process. With an interest in aging and longevity, Dr. Villeponteau started out by studying developmental biology. “If we could understand development, we could understand aging,” he says. Later, his interest turned more toward the gene regulation aspects. While working as a professor at the University of Michigan at the Institute of Gerontology, he received, and accepted, a job offer from Geron Corporation—a Bay Area startup, in the early ‘90s.

“They were working on telomerase, which I was pretty excited about at the time. I joined them when they first started,” he says. “We had an all-out engagement there to clone human telomerase. It had been cloned in other animals but not in humans or mammals.”

If you were to unravel the tip of the chromosome, a telomere is about 15,000 bases long at the moment of conception in the womb. Immediately after conception, your cells begin to divide, and your telomeres begin to shorten each time the cell divides. Once your telomeres have been reduced to about 5,000 bases, you essentially die of old age.

“What you have to know about telomerase is that it’s only on in embryonic cells. In adult cells, it’s totally, for the most part, turned off, with the exception of adult stem cells,” Dr. Villeponteau explains. “Adult stem cells have some telomerase – not full and not like the embryonic stem cells, but they do have some telomerase activity.”

Most of the research currently being done, both in academia and industrial labs, revolves around either embryonic stem cells, or a second type called induced pluripotent stem cells (iPS). Dr. Villeponteau, on the other hand, believes adult stem cells are the easiest and most efficient way to achieve results.

That said, adult stem cells do have their drawbacks. While they’re your own cells, which eliminates the problem of immune-related issues, there’s just not enough of them. Especially as you get older, there are fewer and fewer adult stem cells, and they tend to become increasingly dysfunctional too. Yet another hurdle is that they don’t form the tissues that they need to form…

To solve such issues, Dr. Villeponteau has created a company with the technology and expertise to amplify your adult stem cells a million-fold or more, while still maintaining their ability to differentiate all the different cell types, and without causing the cells to age. Again, it is the adult stem cell’s ability to potentially cure, or at least ameliorate, many of our age-related diseases by regenerating tissue that makes this field so exciting.

Dr Villeponteau believes you can add many years, likely decades, to your life simply by eating right, exercising (which promotes the production of muscle stem cells, by the way) and living an otherwise clean and healthy lifestyle. Extreme life extension, on the other hand, is a different matter.

His book, Decoding Longevity, covers preventive strategies to prolong your life, mainly diet, exercise, and supplements. A portion of the book also covers future developments in the area of more radical life extension, such as stem cell technology.

If you would like to read the entire interview here is a link to the text version:

Transcript of Interview With Dr. Bryant Villeponteau by Dr. Joseph Mercola

lroot on November 15th, 2017

Now researchers have found a way not just to stop, but, reverse the aging process. The key is something called a telomere. We all have them. They are the tips or caps of your chromosomes. They are long and stable in young adults, but, as we age they become shorter, damaged and frayed. When they stop working we start aging and experience things like hearing and memory loss.

In a recent study published in the peer reviewed journal Nature scientists took mice that were prematurely aged to the equivalent of 80-year-old humans, added an enzyme and essentially turned their telomeres back on. After the treatment they were the physiological equivalent of young adults. You can see the before and after pictures in the videos above. Brain function improved, their fertility was restored it was a remarkable reversal of the aging process. In the top video the untreated mouse shows bad skin, gray hair and it is balding. The mouse with it’s telomeres switched back on has a dark coat color, the hair is restored and the coat has a nice healthy sheen to it. Even more dramatic is the change in brain size. Before treatment the aged mice had 75% of a normal size brain like a patient with severe Alzheimers. After the telomeres were reactivated the brain returned to normal size. As for humans while it is just one factor scientists say the longer the telomeres the better the chances for a more graceful aging.

The formal study Telomere dysfunction induces metabolic and mitochondrial compromise was published in Nature.

Additional information published by Harvard can be found in the following articles.

Scientists Find Root Molecular Cause of Declining Health in the Old

Decoding Immortality – Smithsonian Channel Video about the Discovery of Telomerase

While scientists are not yet able to accomplish the same results in humans we believe we have developed a nutraceutical to help prolong youth and possibly extend life until age reversal therapy for humans becomes available.

lroot on November 10th, 2017

New evidence that adult stem cells are critical to human aging has recently been published on a study done on a super-centenarian woman that lived to be 115 years. At death, her circulating stem cell pool had declined to just two active stem cells from stem cell counts that are typically more than a thousand in younger adults. Super-centenarians have survived all the normal diseases that kill 99.9% of us before 100 years of age, so it has been a mystery as to what actually kills these hardy individuals. This recent data suggest that stem cell decline may be the main contributor to aging. If so, stabilizing stem cells may be the best thing one can do to slow your rate of aging.

There are many theories of aging that have been proposed. For example, damage to cells and tissues from oxidative stress has been one of the most popular fundamental theories of aging for more than half a century. Yet antioxidant substances or genes that code antioxidant enzymes have proven largely ineffective in slowing aging when tested in model animals. Thus, interest by scientists has shifted to other hypotheses that might provide a better explanation for the slow declines in function with age.

Stem cells provide one such promising mechanism of aging. Of course, we all know that babies are young and vigorous, independent of the age of their parents. This is because adults have embryonic stem cells that can generate young new cells needed to form a complete young baby. Indeed, these embryonic stem cells are the product of continuously evolving stem cell populations that go back to the beginning of life on earth over 3.5 billion years ago!

In adults, the mostly immortal embryonic stem cells give rise to mortal adult stem cells in all the tissues of the body. These adult stem cells can regenerate your cells and tissues as they wear out and need replacement. Unfortunate, adult stem cells also age, which leads to fewer cells and/or loss of function in cell replacement. As functional stem cells decline, skin and organs decline with age.

Blood from world’s oldest woman suggests life limit

Time Magazine: Long-Life Secrets From The 115-Year-Old Woman

Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis

Abstract
The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole-genome sequencing, we estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-yr-old woman. The detected mutations appear to have been harmless passenger mutations: They were enriched in noncoding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.

lroot on November 8th, 2017

Rat Walks Again

Engineered tissue containing human stem cells has allowed paraplegic rats to walk independently and regain sensory perception. The implanted rats also show some degree of healing in their spinal cords. The research, published in Frontiers in Neuroscience, demonstrates the great potential of stem cells undifferentiated cells that can develop into numerous different types of cells to treat spinal cord injury.

Spinal cord injuries often lead to paraplegia. Achieving substantial recovery following a complete spinal cord tear, or transection, is an as-yet unmet challenge.

Led by Dr. Shulamit Levenberg, of the Technion-Israel Institute of Technology, the researchers implanted human stem cells into rats with a complete spinal cord transection. The stem cells, which were derived from the membrane lining of the mouth, were induced to differentiate into support cells that secrete factors for neural growth and survival.

The work involved more than simply inserting stem cells at various intervals along the spinal cord. The research team also built a three-dimensional scaffold that provided an environment in which the stem cells could attach, grow and differentiate into support cells. This engineered tissue was also seeded with human thrombin and fibrinogen, which served to stabilize and support neurons in the rat’s spinal cord.

Rats treated with the engineered tissue containing stem cells showed higher motor and sensory recovery compared to control rats. Three weeks after introduction of the stem cells, 42% of the implanted paraplegic rats showed a markedly improved ability to support weight on their hind limbs and walk. 75% of the treated rats also responded to gross stimuli to the hind limbs and tail.

In contrast, control paraplegic rats that did not receive stem cells showed no improved mobility or sensory responses.

In addition, the lesions in the spinal cords of the treated rats subsided to some extent. This indicates that their spinal cords were healing.

While the results are promising, the technique did not work for all implanted rats. An important area for further research will be to determine why stem cell implantation worked in some cases but not others. As the research team notes, “This warrants further investigation to shed light on the mechanisms underlying the observed recovery, to enable improved efficacy and to define the intervention optimal for treatment of spinal cord injury.”

Although the study in itself does not solve the challenge of providing medical treatments for spinal cord injury in humans, it nevertheless points the way to that solution. As Dr. Levenberg puts it: “Although there is still some way to go before it can be applied in humans, this research gives hope.”

Reference: Javier Ganz, Erez Shor, Shaowei Guo, Anton Sheinin, Ina Arie, Izhak Michaelevski, Sandu Pitaru, Daniel Offen, Shulamit Levenberg. Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection. Frontiers in Neuroscience, 2017; 11 DOI: 10.3389/fnins.2017.00589

lroot on November 7th, 2017

Telomeres on Ends of DNA

A team led by Professor Lorna Harries, Professor of Molecular Genetics at the University of Exeter, has discovered a new way to rejuvenate inactive senescent cells. Within hours of treatment the older cells started to divide, and had longer telomeres the ‘caps’ on the chromosomes which shorten as we age.

This discovery, funded by the Dunhill Medical Trust, builds on earlier findings from the Exeter group that showed that a class of genes called splicing factors are progressively switched off as we age. The University of Exeter research team, working with Professor Richard Faragher and Dr Elizabeth Ostler from the University of Brighton, found that splicing factors can be switched back on with chemicals, making senescent cells not only look physically younger, but start to behave more like young cells and start dividing.

The researchers applied compounds called resversatrol analogues, chemicals based on a substance naturally found in red wine, dark chocolate, red grapes and blueberries, to cells in culture. These compounds are similar to, but different than resveratrol. The chemicals caused splicing factors, which are progressively switched off as we age to be switched back on. Within hours, the cells looked younger and started to rejuvenate, behaving like young cells and dividing.

The research, Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence, is published in the journal, BMC Cell Biology.

The discovery has the potential to lead to therapies which could help people age better, without experiencing some of the degenerative effects of getting old. Most people by the age of 85 are not very healthy.

This is a step so that people can live normal lifespans, but with health for their entire life. The data suggests that using these compounds to switch back on the major class of genes that are switched off as we age might provide a means to restore function to old cells.

Dr Eva Latorre, Research Associate at the University of Exeter, who carried out the experiments, was surprised by the extent and rapidity of the changes in the cells.

“When I saw some of the cells in the culture dish rejuvenating I couldn’t believe it. These old cells were looking like young cells. It was like magic,” she said. “I repeated the experiments several times and in each case the cells rejuvenated. I am very excited by the implications and potential for this research.”

As we age, our tissues accumulate senescent cells which are alive but do not grow or function as they should. These old cells lose the ability to correctly regulate the output of their genes. This is one reason why tissues and organs become susceptible to disease as we age. When activated, genes make a message that gives the instructions for the cell to behave in a certain way. Most genes can make more than one message, which determines how the cell acts.

Splicing factors are crucial in ensuring that genes can perform their full range of functions. One gene can send out several messages to the body to perform a function such as the decision whether or not to grow new blood vessels and the splicing factors make the decision about which message to make. As people age, the splicing factors tend to work less efficiently or not at all, restricting the ability of cells to respond to challenges in their environment. Senescent cells, which can be found in most organs from older people, also have fewer splicing factors.

Professor Harries added: “This demonstrates that when you treat old cells with molecules that restore the levels of the splicing factors, the cells regain some features of youth. They are able to grow, and their telomeres the caps on the ends of the chromosomes that shorten as we age are now longer, as they are in young cells. Far more research is needed now to establish the true potential for these sort of approaches to address the degenerative effects of ageing. ”

Professor Richard Faragher of the University of Brighton, will today argue for more research into the degenerative effects of ageing in a debate into whether science should be used to extend people’s lifespans.

“At a time when our capacity to translate new knowledge about the mechanisms of aging into medicines and lifestyle advice is limited only by a chronic shortage of funds, older need practical action to restore their health and they need it yesterday,” he said.

Professor Faragher added: “Our discovery of cell rejuvenation using these simple compounds shows the enormous potential of ageing research to improve the lives of older people”.

Stem Cell 100 and Stem Cell 100+ both contain more than one type of natural resveratrol analogue.

Reference: Eva Latorre, Vishal C. Birar, Angela N. Sheerin, J. Charles C. Jeynes, Amy Hooper, Helen R. Dawe, David Melzer, Lynne S. Cox, Richard G. A. Faragher, Elizabeth L. Ostler, Lorna W. Harries. Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence. BMC Cell Biology, 2017; 18 (1) DOI: 10.1186/s12860-017-0147-7

Woman Lifting Dumbbells

Easy strength training exercises which require no equipment such as wall push ups or ordinary push ups could add years to your life according to a new study of over 80,000 adults led by the University of Sydney.

The largest study to compare the mortality outcomes of different types of exercise found people who did strength-based exercise had a 23 percent reduction in risk of premature death by any means, and a 31 percent reduction in cancer-related death.

Lead author Associate Professor Emmanuel Stamatakis from the School of Public Health and the Charles Perkins Centre said while strength training has been given some attention for functional benefits as we age, little research has looked at its impact on mortality.

“The study shows exercise that promotes muscular strength may be just as important for health as aerobic activities like jogging or cycling,” said Associate Professor Stamatakis.

“And assuming our findings reflect cause and effect relationships, it may be even more vital when it comes to reducing risk of death from cancer.”

The World Health Organization’s Physical Activity Guidelines for adults recommend 150 minutes of aerobic activity, plus two days of muscle strengthening activities each week.

Associate Professor Stamatakis said governments and public health authorities have neglected to promote strength-based guidelines in the community, and as such misrepresented how active we are as a nation.

He cites the example of The Australian National Nutrition and Physical Activity Survey which, based on aerobic activity alone, reports inactivity at 53 percent. However, when the World Health Organization’s (WHO) strength-based guidelines are also taken into account, 85 percent of Australians fail to meet recommendations.

“Unfortunately, less than 19 percent of Australian adults do the recommended amount of strength-based exercise,” said Associate Professor Stamatakis.

“Our message to date has just been to get moving but this study prompts a rethink about, when appropriate, expanding the kinds of exercise we are encouraging for long-term health and wellbeing.”

The analysis also showed exercises performed using one’s own body weight without specific equipment were just as effective as gym-based training.

“When people think of strength training they instantly think of doing weights in a gym, but that doesn’t have to be the case.

“Many people are intimidated by gyms, the costs or the culture they promote, so it’s great to know that anyone can do classic exercises like triceps dips, sit-ups, push-ups or lunges in their own home or local park and potentially reap the same health benefits.”

The research, published in the American Journal of Epidemiology today, is based on a pooled population sample of over 80,306 adults with data drawn from the Health Survey for England and Scottish Health Survey, linked with the NHS Central Mortality Register.

The study was observational, however adjustments were made to reduce the influence of other factors such as age, sex, health status, lifestyle behaviours and education level. All participants with established cardiovascular disease or cancer at baseline and those who passed away in the first two years of follow up were excluded from the study to reduce the possibility of skewing results due to those with pre-existing conditions participating in less exercise.

Key findings:

•Participation in any strength-promoting exercise was associated with a 23 percent reduction in all-cause mortality and a 31 percent reduction in cancer mortality

•Own bodyweight exercises that can be performed in any setting without equipment yielded comparable results to gym-based activities

•Adherence to WHO’s strength-promoting exercise guideline alone was associated with reduced risk of cancer-related death, but adherence to the WHO’s aerobic physical activity guideline alone was not

•Adherence to WHO’s strength-promoting exercise and aerobic guidelines combined was associated with a greater risk reduction in mortality than aerobic physical activity alone

•There was no evidence of an association between strength-promoting exercise and cardiovascular disease mortality.

Reference: Emmanuel Stamatakis, I-Min Lee, Jason Bennie, Jonathan Freeston, Mark Hamer, Gary O’Donovan, Ding Ding, Adrian Bauman, Yorgi Mavros. Does strength promoting exercise confer unique health benefits? A pooled analysis of eleven population cohorts with all-cause, cancer, and cardiovascular mortality endpoints. American Journal of Epidemiology, 2017; DOI: 10.1093/aje/kwx345

lroot on October 16th, 2017

Adult Stem Cells

As scientists work to unlock the mysteries of why some 80-year-olds play tennis every week while others must live in nursing homes, researchers with the University of Miami’s Interdisciplinary Stem Cell Institute report they have found the beginnings of what may be the first therapeutic treatment for frailty, a common condition of aging that can lead to falls and other adverse effects. An early stage clinical trial conducted in Miami found that elderly patients breathed easier and walked longer distances after receiving a single infusion of stem cells from young and healthy donors.

Scientists have been making significant headway recently, studying a variety of anti-aging targets from discovering a protein that can restore hair and improve fitness in old mice to revealing how fecal transplants increase the lifespan of some fish. But the arena of stem cell transplantation has offered some of the most exciting anti-aging research outcomes.

Mesenchymal stem cells (MSCs) are a particular type of adult stem cell generating a great deal of interest in the world of science. MSCs are currently being trialed as treatment for no less than a dozen different types of conditions.

The results of two human clinical trials into a stem cell therapy that can reverse symptoms of age-associated frailty have been published, and the indications are that this landmark treatment is both safe and strikingly effective in tackling key factors in aging.

This new MSC treatment is targeted at reducing the effects of frailty on senior citizens. This is the first anti-aging stem cell treatment directed specifically at the problem of age-associated frailty to move close to a final FDA approval stage.

The treatment derives human mesenchymal stem cells from adult donor bone marrow and in these clinical trials involves a single infusion in patients with an average age of 76. Both Phase 1 and Phase 2 human trials have demonstrated the treatment to have no adverse health effects.

Although the two human trials were ostensibly designed to just demonstrate safety they do offer remarkable results in efficacy as well, paving the way for larger, Phase 3 clinical trials.

In the first trial 15 frail patients received a single MSC infusion collected from bone marrow donors aged between 20 and 45 years old. Six months later all patients demonstrated improved fitness outcomes, tumor necrosis factor levels and overall quality of life.

The second trial was a randomized, double blind study with placebo group. Again no adverse affects were reported and physical improvements were noted by the researchers as “remarkable”.

“There are always caveats associated with interpreting efficacy in small numbers of subjects, yet it is remarkable that a single treatment seems to have generated improvement in key features of frailty that are sustained for many months,” writes David G. Le Couter and colleagues in a guest editorial in The Journals of Gerontology praising the research.

The next stage for the research is to move into an expanded Phase 2b clinical trial involving 120 subjects across 10 locations. After that a final, large randomized Phase 3 clinical trial will be the only thing holding the treatment back from final public approval by the FDA.

“With the aging of the population, stem cells hold great promise to treat aging-related disability and frailty, improving physical capacity and quality of life,” says one of the scientists working on the project Joshua M. Hare, Director of the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine.

“There is no FDA approved treatment for aging frailty and an enormous unmet need that will only increase with the changing demographics.”

The results of the Phase 1 and Phase 2 clinical trials were recently published in The Journals of Gerontology.

References

Phase 1 Trial: Samuel Golpanian Darcy L DiFede Aisha Khan Ivonne Hernandez Schulman Ana Marie Landin Bryon A Tompkins Alan W Heldman Roberto Miki Bradley J Goldstein Muzammil Mushtaq Silvina Levis-Dusseau John J Byrnes Maureen Lowery Makoto Natsumeda Cindy Delgado Russell Saltzman Mayra Vidro-Casiano Marietsy V Pujol Moisaniel Da Fonseca Anthony A Oliva, Jr Geoff Green Courtney Premer Audrey Medina Krystalenia Valasaki Victoria Florea Erica Anderson Jill El-Khorazaty Adam Mendizabal Pascal J Goldschmidt-Clermont Joshua M Hare; Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty; The Journals of Gerontology: Series A, Volume 72, Issue 11, 12 October 2017, Pages 1505–1512, https://doi.org/10.1093/gerona/glx056

Phase 2 Trial: Bryon A Tompkins, MD Darcy L DiFede, RN, BSN Aisha Khan, Msc, MBA Ana Marie Landin, PhD Ivonne Hernandez Schulman, MD Marietsy V Pujol, MBA Alan W Heldman, MD Roberto Miki, MD Pascal J Goldschmidt-Clermont, MD Bradley J Goldstein, MD Muzammil Mushtaq, MD Silvina Levis-Dusseau, MD John J Byrnes, MD Maureen Lowery, MD Makoto Natsumeda, MD Cindy Delgado, MA, CCRC Russell Saltzman, BS.Ed Mayra Vidro-Casiano, MPH Moisaniel Da Fonseca, AA Samuel Golpanian, MD Courtney Premer, PhD Audrey Medina, BSc Krystalenia Valasaki, MSc Victoria Florea, MD Erica Anderson, MA Jill El-Khorazaty, MS Adam Mendizabal, PhD Geoff Green, BA, MBA Anthony A Oliva, PhD Joshua M Hare, MD; Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial; The Journals of Gerontology: Series A, Volume 72, Issue 11, 12 October 2017, Pages 1513–1522, https://doi.org/10.1093/gerona/glx137

lroot on October 14th, 2017

Healthy Living

People who are overweight cut their life expectancy by two months for every extra kilogram (2.2 pounds) of weight they carry, research suggests.

A major study of the genes that underpin longevity has also found that education leads to a longer life, with almost a year added for each year spent studying beyond school.

Other key findings are that people who give up smoking, study for longer and are open to new experiences might expect to live longer.

Scientists at the University of Edinburgh analysed genetic information from more than 600,000 people alongside records of their parents’ lifespan.

Because people share half of their genetic information with each of their parents, the team were able to calculate the impact of various genes on life expectancy.

Lifestyle choices are influenced to a certain extent by our DNA/genes, for example, have been linked to increased alcohol consumption and addiction. The researchers were therefore able to work out which have the greatest influence on lifespan.

Their method was designed to rule out the chances that any observed associations could be caused by a separate, linked factor. This enabled them to pinpoint exactly which lifestyle factors cause people to live longer, or shorter, lives.

They found that cigarette smoking and traits associated with lung cancer had the greatest impact on shortening lifespan.

For example, smoking a packet of cigarettes per day over a lifetime knocks an average of seven years off life expectancy, they calculated. But smokers who give up can eventually expect to live as long as somebody who has never smoked.

Body fat and other factors linked to diabetes also have a negative influence on life expectancy.

The study also identified two new DNA differences that affect lifespan. The first is a gene that affects blood cholesterol levels and reduces lifespan by around eight months. The second is a gene linked to the immune system that adds around half a year to life expectancy.

The research, published in Nature Communications, was funded by the Medical Research Council.

Data was drawn from 25 separate population studies from Europe, Australia and North America, including the UK Biobank which is a major study into the role of genetics and lifestyle in health and disease.

Professor Jim Wilson, of the University of Edinburgh’s Usher Institute, said: “The power of big data and genetics allow us to compare the effect of different behaviours and diseases in terms of months and years of life lost or gained, and to distinguish between mere association and causal effect.”

Dr Peter Joshi, Chancellor’s Fellow at the University of Edinburgh’s Usher Institute, said: “Our study has estimated the causal effect of lifestyle choices. We found that, on average, smoking a pack a day reduces lifespan by seven years, whilst losing one kilogram of weight will increase your lifespan by two months.”

Reference: Peter K. Joshi, Nicola Pirastu, […], James F. Wilson. Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. Nature Communications, 2017; 8 (1) DOI: 10.1038/s41467-017-00934-5

Genes

Researchers at the Institute of Molecular Biology (IMB) in Mainz have made a breakthrough in understanding the origin of the aging process. They have identified that genes belonging to a process called autophagy, which is one of the cells most critical survival processes, promote health and fitness in young worms but drive the process of aging later in life. This research published in the journal Genes & Development gives some of the first clear evidence for how the aging process arises as a quirk of evolution. The researchers show that by promoting longevity through shutting down autophagy in old worms there is a strong improvement in neuronal and subsequent whole body health.

Getting old is something that happens to everyone and nearly every species on this planet, but the question is: should it? In a recent publication in the journal Genes & Development titled “Neuronal inhibition of the autophagy nucleation complex extends lifespan in post-reproductive C. elegans,” Dr. Holger Richly’s lab at IMB has found some of the first genetic evidence that may put this question to rest.

According to Jonathan Byrne, co-lead author of the paper: “These AP genes had not been found before because it is incredibly difficult to work with already old animals. We were the first to figure out how to do this on a large scale. From a relatively small screen, we found a surprisingly large number of genes that seem to operate in an antagonistic fashion.” Previous studies had found genes that encourage aging while still being essential for development, but the 30 genes the IMB researchers found represent some of the first found promoting aging specifically only in old worms. “Considering we tested only 0.05 percent of all the genes in a worm this suggests there could be many more of these genes out there to find,” stated Byrne.

According to Thomas Wilhelm, the other co-lead author of the paper. “What was most surprising was what processes those genes were involved in.” Not content to provide just the missing evidence for a 60-year-old puzzle, Wilhelm and his colleagues went on to describe what a subset of these genes do in C. elegans and how they might be driving the aging process. “This is where the results really get fascinating,” emphasized Dr. Holger Richly, the principal investigator of the study. “We found a series of genes involved in regulating autophagy, which accelerate the aging process.” These results are surprising indeed as the process of autophagy is a critical recycling process in the cell and is usually required to live a normal full lifetime. Autophagy is known to become slower with age and the authors of this paper show that it appears to completely deteriorate in older worms. They demonstrate that shutting down key genes in the initiation of the process allows the worms to live longer compared with leaving it running crippled. “This could force us to rethink our ideas about one of the most fundamental processes that exist in a cell,” Richly explained. “Autophagy is nearly always thought of as beneficial even if it is barely working. We instead show that there are severe negative consequences when it breaks down and then you are better off bypassing it all together. It is classic AP: in young worms, autophagy is working properly and is essential to reach maturity, but after reproduction it starts to malfunction causing the worms to age,” he continued.

In a final revelation, Richly and his team were able to track the source of the pro longevity signals to a specific tissue, namely the neurons. By inactivating autophagy in the neurons of old worms they were not only able to prolong the worms life but they increased the total health of the worms dramatically. “Imagine reaching the halfway point in your life and getting a drug that leaves you as fit and mobile as someone half your age and you even live longer. That is what it is like for the worms,” said Thomas Wilhelm. “We turn autophagy off only in one tissue and the whole animal gets a boost. The neurons are much healthier in the treated worms and we think this keeps the muscles and the rest of the body in good shape. The net result is a 50 percent extension of life.”

While the authors do not yet know the exact mechanism causing the neurons to stay healthier for longer, this finding could have wide implications. “It is possible that these autophagy genes could represent a good way to help preserve neuronal integrity in these cases,” elaborated Thomas Wilhelm. While any such treatment would be a long way off, assuming such findings could be recapitulated in humans it offers a tantalising hope for being able to prevent disease and get younger and healthier while doing so.

Reference: Thomas Wilhelm, Jonathan Byrne, Rebeca Medina, Ena Kolundži?, Johannes Geisinger, Martina Hajduskova, Baris Tursun, Holger Richly. Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans. Genes & Development, 2017; 31 (15): 1561 DOI: 10.1101/gad.301648.117

lroot on September 20th, 2017

Nuts

A study recently published in the online version of the European Journal of Nutrition has found that people who include nuts in their diet are more likely to reduce weight gain and lower the risk of overweight and obesity.

The findings came to light after researchers at Loma Linda University School of Public Health and the International Agency for Research on Cancer (IARC) evaluated diet and lifestyle data from more than 373,000 individuals from 10 European countries between the ages of 25 and 70.

Senior investigator Joan Sabaté, MD, DrPH, director of the Center for Nutrition, Lifestyle and Disease Prevention at LLUSPH, said that many people have historically assumed that nuts an energy-dense, high-fat food are not a good choice for individuals who want to lose weight. The findings, however, contradict that assumption.

In their five-year study, Sabaté and junior investigator Heinz Freisling, PhD, a nutritional epidemiologist with the Nutritional Methodology and Biostatistics group at IARC headquarters in Lyons, France, found that participants gained a mean average of 2.1 kilograms during the five-year period of the study. However, participants who ate the most nuts not only had less weight gain than their nut-abstaining peers, but also enjoyed a 5 percent lower risk of becoming overweight or obese.

“To me, this confirms that nuts are not an obesogenic food,” Sabaté said.

The pair of researchers has evaluated nuts in the past and found that they are positively associated with a variety of health benefits, including healthy aging and memory function in seniors. This study, however, represents the first time they have investigated the relationship between nuts and weight on a large scale. Tree nuts included in the study were almonds, hazelnuts, pistachios and walnuts.

The team analyzed information on the dietary practices and body mass indexes of 373,293 participants, working with data gathered by the European Prospective Investigation into Cancer and Nutrition. Although Sabaté and Freisling extracted and analyzed the data and reported the findings, they were joined by 35 other research scientists from 12 European countries and Malaysia who reviewed the paper ahead of publication.

Sabaté recommends that people eat nuts more often, pointing out that they offer energy, good fats, protein, vitamins, minerals and phytochemicals.

“Eat nuts during your meal,” he suggested. “Put them at the center of your plate to replace animal products. They’re very satiating.”

Reference: Heinz Freisling, Hwayoung Noh, Nadia Slimani, Véronique Chajès, Anne M. May, Petra H. Peeters, Elisabete Weiderpass, Amanda J. Cross, Guri Skeie, Mazda Jenab, Francesca R. Mancini, Marie-Christine Boutron-Ruault, Guy Fagherazzi, Verena A. Katzke, Tilman Kühn, Annika Steffen, Heiner Boeing, Anne Tjønneland, Cecilie Kyrø, Camilla P. Hansen, Kim Overvad, Eric J. Duell, Daniel Redondo-Sánchez, Pilar Amiano, Carmen Navarro, Aurelio Barricarte, Aurora Perez-Cornago, Konstantinos K. Tsilidis, Dagfinn Aune, Heather Ward, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Giovanna Masala, Claudia Agnoli, Franco Berrino, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, H. Bas Bueno-de-Mesquita, Ulrika Ericson, Emily Sonestedt, Anna Winkvist, Tonje Braaten, Isabelle Romieu, Joan Sabaté. Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study. European Journal of Nutrition, 2017; DOI: 10.1007/s00394-017-1513-0