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.
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.
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.
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.
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.
Recent studies have shown that added sugars, particularly those containing fructose, are a principal driver of diabetes and pre-diabetes, even more so than other carbohydrates. Clinical experts writing in Mayo Clinic Proceedings challenge current dietary guidelines that allow up to 25% of total daily calories as added sugars, and propose drastic reductions in the amount of added sugar, and especially added fructose, people consume.
Worldwide, approximately one in ten adults has type 2 diabetes, with the number of individuals afflicted by the disease across the globe more than doubling from 153 million in 1980 to 347 million in 2008. In the United States, 29 million adults (one in eleven) have type 2 diabetes and another 86 million (more than one in three) have pre-diabetes.
“At current levels, added-sugar consumption, and added-fructose consumption in particular, are fueling a worsening epidemic of type 2 diabetes,” said lead author James J. DiNicolantonio, PharmD, a cardiovascular research scientist at Saint Luke’s Mid America Heart Institute, Kansas City, MO. “Approximately 40% of U.S. adults already have some degree of insulin resistance with projections that nearly the same percentage will eventually develop frank diabetes.”
The net result of excess consumption of added fructose is derangement of both overall metabolism and global insulin resistance say the authors. Other dietary sugars not containing fructose seem to be less detrimental in these respects. Indeed, several clinical trials have shown that compared to glucose or starch, isocaloric exchange with fructose or sucrose leads to increases in fasting insulin, fasting glucose, and the insulin/glucose responses to a sucrose load. “This suggests that sucrose (in particular the fructose component) is more harmful compared to other carbohydrates,” added Dr. DiNicolantonio. Dr. DiNicolantonio and his co-authors, James H O’Keefe, MD, Saint Luke’s Mid America Heart Institute, Kansas City, MO, and Sean C. Lucan, MD, MPH, MS, a family physician at Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, examined animal experiments and human studies to come to their conclusions.
Data from recent trials suggest that replacing glucose-only starch with fructose-containing table sugar (sucrose) results in significant adverse metabolic effects. Adverse effects are broader with increasing baseline insulin resistance and more profound with greater proportions of added fructose in the diet.
The totality of the evidence is compelling to suggest that added sugar, and especially added fructose (usually in the form of high-fructose corn syrup and table sugar), are a serious and growing public health problem, according to the authors.
The 2010 Dietary Guidelines for Americans say it is acceptable for some people to consume up to 19% of calories from added sugars, and the Institute of Medicine permits up to 25% of total calories from added sugars. In contrast, the World Health Organization recommends that added sugars should make up no more than 10% of an entire day’s caloric intake, with a proposal to lower this level to 5% or less for optimal health. Such levels would be more in line with what the authors would recommend and similarly restrictive to existing American Heart Association (AHA) recommendations–to consume no more than six teaspoons (24 grams) of sugar per day for women and no more than nine teaspoons (36 grams) of sugar per day for men.
While fructose is found naturally in some whole foods like fruits and vegetables, consuming these foods poses no problem for human health. Indeed, consuming fruits and vegetables is likely protective against diabetes and broader cardiometabolic dysfunction, explained DiNicolantonio and colleagues. The authors propose that dietary guidelines should be modified to encourage individuals to replace processed foods, laden with added sugars and fructose, with whole foods like fruits and vegetables. “Most existing guidelines fall short of this mark at the potential cost of worsening rates of diabetes and related cardiovascular and other consequences,” they wrote.
The authors also think there should be incentives for industry to add less sugars, especially fructose-containing varieties, to food-and-beverage products. And they conclude that at “an individual level, limiting consumption of foods and beverages that contain added sugars, particularly added fructose, may be one of the single most effective strategies for ensuring one’s robust future health.”
A new procedure can quickly and efficiently increase the length of human telomeres, the protective caps on the ends of chromosomes that are linked to aging and disease, according to scientists at the Stanford University School of Medicine. It causes a significant increase in telomere length soon after the procedure, but does not continue to increase length unless it is done again at a later date. This is a major advantage since it give researchers and potentially later on medical doctors the ability to control the degree of telomere lengthening.
Treated cells behave as if they are much younger than untreated cells, multiplying with abandon in the laboratory dish rather than stagnating or dying.
The procedure, which involves the use of a modified type of RNA, will improve the ability of researchers to generate large numbers of cells for study or drug development, the scientists say. Skin cells with telomeres lengthened by the procedure were able to divide up to 40 more times than untreated cells. The research may point to new ways to treat diseases and aging caused by shortened telomeres.
Telomeres are the protective caps on the ends of the strands of DNA called chromosomes, which house our genomes. In young humans, telomeres are about 8,000-10,000 nucleotides long. They shorten with each cell division, however, and when they reach a critical length the cell stops dividing or dies. This internal “clock” makes it difficult to keep most cells growing in a laboratory for more than a few cell doublings.
‘Turning back the internal clock’
“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life,” said Helen Blau, PhD, professor of microbiology and immunology at Stanford and director of the university’s Baxter Laboratory for Stem Cell Biology. “This greatly increases the number of cells available for studies such as drug testing or disease modeling.”
A paper describing the research was published today in the FASEB Journal. Blau, who also holds the Donald E. and Delia B. Baxter Professorship, is the senior author. Postdoctoral scholar John Ramunas, PhD, of Stanford shares lead authorship with Eduard Yakubov, PhD, of the Houston Methodist Research Institute.
The researchers used modified messenger RNA to extend the telomeres. RNA carries instructions from genes in the DNA to the cell’s protein-making factories. The RNA used in this experiment contained the coding sequence for TERT, the active component of a naturally occurring enzyme called telomerase. Telomerase is expressed by stem cells, including those that give rise to sperm and egg cells, to ensure that the telomeres of these cells stay in tip-top shape for the next generation. Most other types of cells, however, express very low levels of telomerase.
Transient effect an advantage
The newly developed technique has an important advantage over other potential methods: It’s temporary. The modified RNA is designed to reduce the cell’s immune response to the treatment and allow the TERT-encoding message to stick around a bit longer than an unmodified message would. But it dissipates and is gone within about 48 hours. After that time, the newly lengthened telomeres begin to progressively shorten again with each cell division.
The transient effect is somewhat like tapping the gas pedal in one of a fleet of cars coasting slowly to a stop. The car with the extra surge of energy will go farther than its peers, but it will still come to an eventual halt when its forward momentum is spent. On a biological level, this means the treated cells don’t go on to divide indefinitely, which would make them too dangerous to use as a potential therapy in humans because of the risk of cancer.
The researchers found that as few as three applications of the modified RNA over a period of a few days could significantly increase the length of the telomeres in cultured human muscle and skin cells. A 1,000-nucleotide addition represents a more than 10 percent increase in the length of the telomeres. These cells divided many more times in the culture dish than did untreated cells: about 28 more times for the skin cells, and about three more times for the muscle cells.
“We were surprised and pleased that modified TERT mRNA worked, because TERT is highly regulated and must bind to another component of telomerase,” said Ramunas. “Previous attempts to deliver mRNA-encoding TERT caused an immune response against telomerase, which could be deleterious. In contrast, our technique is nonimmunogenic. Existing transient methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse telomere shortening that occurs over more than a decade of normal aging. This suggests that a treatment using our method could be brief and infrequent.”
Potential uses for therapy
“This new approach paves the way toward preventing or treating diseases of aging,” said Blau. “There are also highly debilitating genetic diseases associated with telomere shortening that could benefit from such a potential treatment.”
Blau and her colleagues became interested in telomeres when previous work in her lab showed that the muscle stem cells of boys with Duchenne muscular dystrophy had telomeres that were much shorter than those of boys without the disease. This finding not only has implications for understanding how the cells function — or don’t function — in making new muscle, but it also helps explain the limited ability to grow affected cells in the laboratory for study.
The researchers are now testing their new technique in other types of cells.
“This study is a first step toward the development of telomere extension to improve cell therapies and to possibly treat disorders of accelerated aging in humans,” said John Cooke, MD, PhD. Cooke, a co-author of the study, formerly was a professor of cardiovascular medicine at Stanford. He is now chair of cardiovascular sciences at the Houston Methodist Research Institute.
“We’re working to understand more about the differences among cell types, and how we can overcome those differences to allow this approach to be more universally useful,” said Blau, who also is a member of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.
Eating one avocado a day as part of a heart healthy, cholesterol-lowering moderate-fat diet can help improve bad cholesterol levels in overweight and obese individuals, according to new research published in the Journal of the American Heart Association.
Researchers evaluated the effect avocados had on traditional and novel cardiovascular risk factors by replacing saturated fatty acids from an average American diet with unsaturated fatty acids from avocados.
Forty-five healthy, overweight or obese patients between the ages of 21 and 70 were put on three different cholesterol-lowering diets. Participants consumed an average American diet (consisting of 34 percent of calories from fat, 51 percent carbohydrates, and 16 percent protein) for two weeks prior to starting one of the following cholesterol lowering diets: lower fat diet without avocado, moderate-fat diet without avocado, and moderate-fat diet with one avocado per day. The two moderate fat diets both provided 34 percent of calories as fat (17 percent of calories from monounsaturated fatty acids/MUFAs), whereas the lower fat diet provided 24 percent of calories as fat (11 percent from MUFAs). Each participant consumed each of the three test diet for five weeks. Participants were randomly sequenced through each of the three diets.
•Compared to the baseline average American diet, low-density lipoprotein (LDL) — the so called ‘bad cholesterol’ — was 13.5 mg/dL lower after consuming the moderate fat diet that included an avocado. LDL was also lower on the moderate fat diet without the avocado (8.3 mg/dL lower) and the lower fat diet (7.4 mg/dL lower), though the results were not as striking as the avocado diet.
•Several additional blood measurements were also more favorable after the avocado diet versus the other two cholesterol-lowering diets as well: total cholesterol, triglycerides, small dense LDL, non-HDL cholesterol, and others.
These measurements are all considered to be cardio-metabolic risk factors in ways that are independent of the heart-healthy fatty acid effects, said Penny M. Kris-Etherton, Ph.D., R.D., senior study author and Chair of the American Heart Association’s Nutrition Committee and Distinguished Professor of Nutrition at Pennsylvania State University, in University Park, Pennsylvania.
“This was a controlled feeding study, but that is not the real-world — so it is a proof-of-concept investigation. We need to focus on getting people to eat a heart-healthy diet that includes avocados and other nutrient-rich food sources of better fats,” Kris-Etherton said.
“In the United States avocados are not a mainstream food yet, and they can be expensive, especially at certain times of the year. Also, most people do not really know how to incorporate them in their diet except for making guacamole. But guacamole is typically eaten with corn chips, which are high in calories and sodium. Avocados, however, can also be eaten with salads, vegetables, sandwiches, lean protein foods (like chicken or fish) or even whole.”
For the study researchers used Hass avocados, the ones with bumpy green skin. In addition to MUFAs, avocados also provided other bioactive components that could have contributed to the findings such as fiber, phytosterols, and other compounds.
According to researchers, many heart-healthy diets recommend replacing saturated fatty acids with MUFAs or polyunsaturated fatty acids to reduce the risk of heart disease. This is because saturated fats can increase bad cholesterol levels and raise the risk of cardiovascular disease.
The Mediterranean diet, includes fruits, vegetables, whole grains, fatty fish, and foods rich in monounsaturated fatty acids–like extra-virgin olive oil and nuts. Like avocados, some research indicates that these not only contain better fats but also certain micronutrients and bioactive components that may play an important role in reducing risk of heart disease.
After I first learned about the massive number of people suffering from Vitamin D deficiency I went to my doctor and had a blood test called 25-hydroxyvitamin D. I expected that since I have a very healthy diet, take lots of supplements and exercise outdoors (with sunscreen) that my level would be high. It turned out that my blood showed a low level of Vitamin D. Our main source is sun exposure, yet it is a double edged sword since being exposed to the sun without sunscreen can cause skin damage, premature aging of the skin and other more serious problems. When wearing sunscreen your body can’t make much Vitamin D. I started taking 5000 IU/day of Vitamin D3 and after a few months I tested in the middle of the normal range. I have continued to take that much Vitamin D for years now and my yearly blood tests continue to be in the middle of the normal range. Everyone is different so the recommendation is to get tested and if you are low take at least 1000 IU of Vitamin D3/day or even as much as 5000 IU/day depending upon your blood test results and your doctors recommendations. Given the large amount of time that most people spend indoors combined with the use of sunscreen the RDA of 400 IU of Vitamin D is not enough for a massive number of people.
Following is a summary of the article “The Vitamin D Epidemic and its Health Consequences” that was published in The Journal of Nutrition.
“Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the collagen matrix in young children’s bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one’s vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination. ”
“Vitamin D, known as the “sunshine vitamin,” has been taken for granted and, until recently, little attention has been focused on its important role for adult bone health and for the prevention of many chronic diseases. It has been assumed that vitamin D deficiency is no longer a health issue in the United States and Europe. However, it is now recognized that everyone is at risk for vitamin D deficiency.”
The full article published in The Journal of Nutrition can be found here: http://jn.nutrition.org/content/135/11/2739S.full
In a study of more than 17,000 Canadians published in 2009 by Dr Peter Katzmarzyk and colleagues at the Pennington Biomedical Research Center they found links between time spent sitting and mortality. “Individuals who sat the most were roughly 50% more likely to die during the follow-up period than individuals who sat the least, even after controlling for age, smoking, and physical activity levels.”
Now new research suggests that taking short but frequent walks can counteract the harm caused by sitting for long periods of time.
The researchers found that even just a five-minute stroll can help.
“American adults sit for approximately eight hours a day,” study author Saurabh Thosar, now a postdoctoral researcher at Oregon Health & Science University, said in an Indiana University news release. “The impairment in endothelial function is significant after just one hour of sitting. It is interesting to see that light physical activity can help in preventing this impairment.”
According to background information from Indiana University, sitting for a prolonged period of time can cause blood to pool in the legs. This happens because muscles are not contracting and pumping blood to the heart as effectively. As a result, the ability of blood vessels to expand from increased blood flow can become impaired. Being sedentary is also linked to high cholesterol and a larger waistline, which increase the risk for heart and metabolic disease.
“There is plenty of epidemiological evidence linking sitting time to various chronic diseases and linking breaking sitting time to beneficial cardiovascular effects, but there is very little experimental evidence,” said Thosar, who was a doctoral candidate at IU’s School of Public Health-Bloomington when the study was conducted. “We have shown that prolonged sitting impairs endothelial function, which is an early marker of cardiovascular disease, and that breaking sitting time prevents the decline in that function.”
The researchers examined the effects of three hours of sitting on 11 healthy men who were not obese. The men, who ranged in age from 20 to 35 years old, participated in two trials.
First, the men sat for three hours without moving their legs. When the study began and once every hour afterwards, the function of their femoral artery was measured with a blood pressure cuff and ultrasound technology.
During the second trial, the men sat for three hours but also walked on a treadmill for five minutes after 30 minutes, 1.5 hours and 2.5 hours. The men walked at a slow pace of 2 miles per hour. The function of their femoral artery was again measured with a blood pressure cuff and ultrasound technology.
Overall, the researchers found, the ability of the arteries in the legs to expand was reduced by as much as 50 percent after just one hour of sitting. The men who walked for five minutes for each hour they spent sitting, however, had no reduction in the function of their arteries during the three-hour period.
The researchers concluded that the increased muscle activity and blood flow from the small amount of exercise offset the negative impacts of sitting.
By Mary Elizabeth Dallas in HealthDay News. The research was published Sept. 8 in the journal Medicine & Science in Sports & Exercise.
UCLA biologists have identified a gene that can slow the aging process throughout the entire body when activated remotely in key organ systems.
Working with fruit flies, the life scientists activated a gene called AMPK that is a key energy sensor in cells; it gets activated when cellular energy levels are low.
Increasing the amount of AMPK in fruit flies’ intestines increased their lifespans by about 30 percent to roughly eight weeks from the typical six weeks and the flies stayed healthier longer as well.
Stem Cell 100TM and Stem Cell 100+TM both contain several compounds that activate AMPK. They also act on a number of additional anti-aging pathways which allowed us to double fruit fly lifespan as well as greatly increase their healthspan (the length of time they were healthy and active).
The research, published in the open-source journal Cell Reports, could have important implications for delaying aging and disease in humans, said David Walker, an associate professor of integrative biology and physiology at UCLA and senior author of the research.
“We have shown that when we activate the gene in the intestine or the nervous system, we see the aging process is slowed beyond the organ system in which the gene is activated,” Walker said.
Walker said that the findings are important because extending the healthy life of humans would presumably require protecting many of the body’s organ systems from the ravages of aging, but delivering anti-aging treatments to the brain or other key organs could prove technically difficult. The study suggests that activating AMPK in a more accessible organ such as the intestine, for example, could ultimately slow the aging process throughout the entire body, including the brain.
Humans have AMPK, but it is usually not activated at a high level, Walker said.
“The ultimate aim of our research is to promote healthy aging in people.”
The fruit fly, Drosophila melanogaster, is a good model for studying aging in humans because scientists have identified all of the fruit fly’s genes and know how to switch individual genes on and off. The biologists studied approximately 100,000 of them over the course of the study.
Lead author Matthew Ulgherait, who conducted the research in Walker’s laboratory as a doctoral student, focused on a cellular process called autophagy, which enables cells to degrade and discard old, damaged cellular components. By getting rid of that “cellular garbage” before it damages cells, autophagy protects against aging, and AMPK has been shown previously to activate this process.
Ulgherait studied whether activating AMPK in the flies led to autophagy occurring at a greater rate than usual.
“A really interesting finding was when Matt activated AMPK in the nervous system, he saw evidence of increased levels of autophagy in not only the brain, but also in the intestine,” said Walker, a faculty member in the UCLA College. “And vice versa: Activating AMPK in the intestine produced increased levels of autophagy in the brain and perhaps elsewhere, too.”
“Matt moved beyond correlation and established causality,” he said. “He showed that the activation of autophagy was both necessary to see the anti-aging effects and sufficient; that he could bypass AMPK and directly target autophagy.”
In research published last year, Walker and his colleagues identified another gene, called parkin, which delayed the onset of aging and extended the healthy life span of fruit flies.
By 2050, the number of people over the age of 80 will triple globally, which could come at great cost to individuals and economies. In a commentary published July 24 in Nature, three experts call for moving forward with preclinical and clinical strategies for people that have been shown to delay aging in animals. In addition to promoting a healthy diet and regular exercise, these strategies include slowing the metabolic and molecular causes of human aging, such as the incremental accumulation of cellular damage that occurs over time.
Unfortunately, medicine focuses almost entirely on fighting chronic diseases in a piecemeal fashion as symptoms develop. Instead, more efforts should be directed to promoting interventions that have the potential to prevent multiple chronic diseases and extend healthy lifespans.
The researchers, at Washington University School of Medicine in St. Louis, Brescia University in Italy, the Buck Institute for Aging and Research and the Longevity Institute at the University of Southern California, write that unfortunately, economic incentives in biomedical research and health care reward treating disease more than promoting good health.
The problems of old age come as a package. More than 70% of people over 65 have two or more chronic conditions. Studies of diet, genes and drugs indicate that delaying one age-related disease probably staves off others. At least a dozen molecular pathways seem to set the pace of physiological ageing.
Researchers have tweaked these pathways to give rodents long and healthy lives. Restricting calorie intake in mice or introducing mutations in nutrient-sensing pathways can extend lifespans by as much as 50%. And these ‘Methuselah mice’ are more likely than controls to die without any apparent diseases. In other words, extending lifespan also seems to increase ‘healthspan’, the time lived without chronic age-related conditions.
Research has highlighted potential benefits from dietary restriction in extending healthy life span. People who eat significantly fewer calories, while still getting optimal nutrition, have “younger,” more flexible hearts. They also have significantly lower blood pressure, much less inflammation in their bodies and their skeletal muscles function in ways similar to muscles in people who are significantly younger.
These insights have made hardly a dent in human medicine. Biomedicine takes on conditions one at a time. Rather, it should learn to stall incremental cellular damage and changes that eventually yield several infirmities.
The current tools for extending healthy life — better diets and regular exercise — are effective. But there is room for improvement, especially in personalizing treatments. Molecular insights from animals should be tested in humans to identify interventions to delay ageing and associated conditions. Together, preclinical and clinical researchers must develop meaningful endpoints for human trials.
Longevity pathways identified in model organisms seem to be conserved in humans and can be manipulated in similar ways. Genetic surveys of centenarians implicate hormonal and metabolic systems. Long-term calorie restriction in humans induces drastic metabolic and molecular changes that resemble those of younger people, notably in inflammatory and nutrient-sensing pathways. Mice engineered to have reduced signalling in these pathways live longer.
Several molecular pathways that increase longevity in animals are affected by approved and experimental drugs. The sirtuin proteins, involved in a similar range of cellular processes, are activated by high concentrations of naturally occurring compounds and extend lifespan in metabolically abnormal obese mice. A plethora of natural and synthetic molecules affect pathways that are shared by ageing and conditions related to ageing.
Diet has similar effects. The drugs rapamycin and metformin mimic changes observed in animals fed calorie and protein-restricted diets. And fasting triggers cellular responses that boost stress resistance, and reduce oxidative damage and inflammation. In rodents, fasting protects against diabetes, cancer, heart disease and neurodegeneration9. There are many anti-ageing interventions that could be considered for clinical trials.
Scientists are not set up to capitalize on these leads to combat the looming ageing crisis. Clinicians do not realize how much is understood about the molecular mechanisms of ageing and its broad effects on diseases. Researchers of all stripes focus too much on easing or reversing the progression of diseases.
The problem is calcified by the funding gap. Budgets for ageing research are small compared to disease-centred research. The Division of Aging Biology in the US National Institute on Aging receives less than 1% of the National Institutes of Health’s budget even though it supports research into the mechanisms underlying most disabilities and chronic diseases. Most grants focus on diseases of specific systems. Most study sections are not set up to evaluate multidisciplinary research on healthspan. The situation is similar in Europe and Japan.
How should we test interventions that extend healthspan? Human data from dietary restriction and genetic-association studies of healthy ageing could help to channel the most promising pathways identified in preclinical studies. Animal studies should be designed to better mimic human ageing. For example, frailty indices are often used in human studies. Comparable indices should be developed for mice.
Suitable endpoints for human trials are needed. Animal work suggests many candidates as potential biomarkers, such as accumulation of molecular damage to DNA, proteins and lipids from oxidative stress. Publicly funded clinical trials could also collect crucial samples of blood, muscle and fat for molecular analysis.
Funding agencies should establish committees of translational scientists to review which markers of biological ageing are most consistent between animals and humans, and prioritize the most practical for further assessment. Chosen biomarkers could be evaluated in clinical studies over a broad age range of patients already being treated with drugs that increase lifespan in animal models. Assessments must also be developed for dietary or other interventions that do not involve drugs.
The most important change must be in mindset. Economic incentives in both biomedical research and health care reward treating diseases more than promoting health. The launch of a few anti-ageing biotech companies such as Calico, created last year by Google, is promising. But public money must be invested in extending healthy lifespan by slowing ageing. Otherwise we will founder in a demographic crisis of increased disability and escalating health-care costs.