Metformin As A Tool To Target Aging
2Wake Forest Older Americans Independence Center and the Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA 2Wake Forest Older Americans Independence Center and the Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA 1Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA 2Wake Forest Older Americans Independence Center and the Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA The publisher's final edited version of this article is available at Cell Metab See other articles in PMC that cite the published article. Aging has been targeted by genetic and dietary manipulation and by drugs in order to increase lifespan and health span in numerous models. Metformin, which has demonstrated protective effects against several age-related diseases in humans, will be tested in the TAME (Targeting Aging with Metformin) trial, as the initial step in the development of increasingly effective next-generation drugs. Over the past decades, remarkable progress has occurred in the science of aging in model organisms. Studies have demonstrated that genetic pathways modulate healthy lifespan in diverse species across great evolutionary distance and established that aging-related pathways constitute a target for intervention ( Barzilai et al., 2012 ; Longo et al., 2015 ). Lifespan has been verifiably modulated by genetic, pharmacologic, and dietary interventions in multiple model systems. With support from an R24 grant from the NIA (J. Kirkland, N.B., S. Austad), we gathered gerontologists with expertise in the biology of aging and in clinical geriatrics to discuss ways to target aging in humans. This effort resulted in the design of the study Targeting Agin Continue reading >>
How Metformin Might Slow Down Aging In Humans | Asian Scientist Magazine | Science, Technology And Medical News Updates From Asia
How Metformin Might Slow Down Aging In Humans Metformin might be able to prevent aging in human cells by acting through the Nrf2-GPx7 pathway, researchers say. AsianScientist (Apr. 27, 2018) In a study published in Aging Cell, researchers in China have shown that the diabetes drug metformin can extend the lifespan of human cells in vitro. Metformin is an FDA-approved drug that has been used for over 60 years to treat type 2 diabetes. In recent years, metformin has been shown to extend the lifespan in some animal models. However, whether metformin can suppress human cellular aging and the mechanisms underlying its probable effects in humans remain unclear. In the present study, a team of researchers led by Professors Wang Chihchen and Liu Guanghui at the Institute of Biophysics of Chinese Academy of Sciences (CAS) found that chronic low-dose metformin treatment delays aging in human cells, specifically diploid fibroblasts and mesenchymal stem cells. Previous research by the same group showed that a protein called endoplasmic reticulum-localized glutathione peroxidase 7 (GPx7) is a key enzyme involved in regulating protein folding and maintaining redox homeostasis. The researchers found that low-dose metformin treatment upregulates the expression of endoplasmic reticulum-localized GPx7 by activating a transcription factor called Nrf2. The levels of GPx7 decrease as cells age and knocking down GPx7 accelerated the process of aging, the researchers said. Interestingly, the metformin-Nrf2-GPx7 axis is known to be involved in worm aging and the worm ortholog of human GPx7 is required for the positive effects of metformin on life span extension in worms. Taken together, these results highlight the importance of the Nrf2-GPx7 pathway in pro-longevity signaling and provide furt Continue reading >>
Metformin Reduces Glucose Intolerance Caused By Rapamycin Treatment In Genetically Heterogeneous Female Mice
Metformin reduces glucose intolerance caused by rapamycin treatment in genetically heterogeneous female mice 1Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio TX 78294, USA 2The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio TX 78229, USA 1Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio TX 78294, USA 2The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio TX 78229, USA 2The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio TX 78229, USA 1Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio TX 78294, USA 2The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio TX 78229, USA 3Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio TX 78229, USA 1Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio TX 78294, USA 2The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio TX 78229, USA 4Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio TX 78229, USA 1Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio TX 78294, USA 2The Sam and Ann Barshop Institute for Longevity and Aging Studies, The Uni Continue reading >>
Metformin In Longevity Study (miles)
Metformin, an FDA approved first-line drug for the treatment of type 2 diabetes, has known beneficial effects on glucose metabolism. Evidence from animal models and in vitro studies suggest that in addition to its effects on glucose metabolism, metformin may influence metabolic and cellular processes associated with the development of age-related conditions, such as inflammation, oxidative damage, diminished autophagy, cell senescence and apoptosis. As such, metformin is of particular interest in clinical translational research in aging since it may influence fundamental aging factors that underlie multiple age-related conditions. The investigators therefore propose a pilot study to examine the effect of metformin treatment on the biology of aging in humans. Namely, whether treatment with metformin will restore the gene expression profile of older adults with impaired glucose tolerance (IGT) to that of young healthy subjects. Aging in humans is a well-established primary risk factor for many disabling diseases and conditions, among them diabetes, cardiovascular disease, Alzheimer's disease and cancer. In fact, the risk of death from these causes is dramatically accelerated (100-1000 fold) between the ages of 35 and 85 years. For this reason, there is a need for the development of new interventions to improve and maintain health into old age - to improve "healthspan". Several mechanisms have been shown to delay the aging process, resulting in improved healthspan in animal models, including mammals. These include caloric restriction, alteration in GH/IGF1 pathways, as well as use of several drugs such as resveratrol (SIRT1 activator) and rapamycin (mTOR inhibitor). At Einstein, the investigators have been working to discover pathways associated with exceptional longevity. Continue reading >>
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The Most Effective Personal Anti-aging Program
The Most Effective Personal Anti-aging Program What are the most effective things you can do to slow the aging process and extend your life expectancy? This is the question being asked by a clinical trial that I am organizing, and which seems to be rapidly taking shape. But before the study begins, we have to have candidates to evaluate. We should begin with hypotheses about what we are evaluating. My idea is to consult some experienced experts, and also to crowd-source this choice, and to ask for your help in selecting the supplements and life habits to be evaluated. Details of the trial were described in two blog posts last spring [ One , Two ] and a more technical manuscript submitted in May. Outcome will be evaluated based on a variant of DNA PhenoAge , taken from a blood test before, amid, and after the two-year trial. We use methylation pattern differences rather than mortality or health outcomes because the latter take a long time to reveal themselves, and make anti-aging trials prohibitively expensive. Using methylation clocks as an endpoint is a new idea, and we dont know if it will work, but if it does, it will be 100 times cheaper and 10 times faster than previous methods. We will have enough bandwidth to test a dozen different measures at once, which itself is a revolutionary step. Many measures are known that are thought to increase life expectancy by a year or a few years each. Of course, we want to know which ones offer their greatest benefits. But even more important, we want to know how they interact, synergize, and interfere with one another. If any one of these measures offered major benefitssay 20 years of lifeits effects would be so apparent that we would probably know it already. Likewise, if these measures added up to 20 years of extra life, we w Continue reading >>
Why A Drug For Aging Would Challenge Washington
Why a drug for aging would challenge Washington It sounds like a dream, until you try to navigate the regulations—and the cost. What if you could live to 85, 90 or even 100 with your mental faculties intact, able to live independently without debilitating conditions until the last year of your life? What if just one medical treatment could stave off a handful of terrifying ailments like heart disease, cancer and Alzheimer’s? The idea of a pill for aging sounds like science fiction or fantasy. But the hunt is increasingly real. At the cutting edge of research, scientists and doctors are already deep into the quest for a drug that could transform the experience of aging. The goal isn’t a pharmaceutical fountain of youth, exactly; nobody is promising to stretch human lifespans indefinitely. Instead, they're looking for a way to ensure healthier aging—a drug that could make it more likely people reach their eighth or ninth decade of life with fewer of the ailments that make old age painful and disabling for millions, and cripplingly expensive for the health care system. The leading approach even has a name: senolytic drugs. The science is still far from proven; it may turn out that like many new ideas, these drugs never show up in American medicine cabinets at all. But the prospect of a drug for healthier aging has already attracted significant investment from well-known drug companies, and the first human studies of anti-aging drugs are getting underway. If the results pan out, the first drugs could be available in as little as a decade. As the research moves forward, however, it is raising a series of new questions that both medicine and regulators will need to confront. And the most complex questions arise around exactly the issue that makes the field so excitin Continue reading >>
Will Metformin Become The First Anti-aging Drug?
A committed group of scientists is seeking to validate metformin as the first-ever anti-aging medication.1,2 In this day of staggering drug prices, metformin is available as a low-cost generic. One mechanism by which metformin works is by activating AMPK, an enzyme inside cells that lowers blood sugar by promoting energy utilization. Activating AMPK has broad-ranging effects that extend far beyond blood sugar control. Studies show that boosting AMPK activity can prevent—and even reverse—the life-shortening effects of aging, such as cardiovascular disease, diabetes, neurodegenerative diseases, cancer, and more.3 In this article, we’ll review data that persuaded the FDA to allow metformin to be studied in humans as the first anti-aging drug.1 Broad-Spectrum Effects The most commonly prescribed antidiabetic drug is metformin. It has been in use in England since 1958 and in the United States since 1995. Derived from a compound found in the French Lilac, metformin has a track record of safety and effectiveness at routine doses of up to 2,000 mg daily.4-7 So what evidence is there for the FDA to consider this drug as an anti-aging medication? The reason is simple: Metformin can block or diminish many of the fundamental factors that accelerate aging.8-12 These include protecting against DNA damage glycation, poor mitochondrial function, and chronic inflammation. Metformin has been shown to facilitate DNA repair, which is critical for cancer prevention. By attacking these fundamental degenerative processes, metformin can prevent the development of aging’s most troubling diseases. Metformin has also been shown to increase the production of known longevity-promoting signaling molecules in cells, such as mTOR and AMPK—all of which reduce fat and sugar storage and increas Continue reading >>
Metformin For Protection Against Alzheimer's, Cancer And Heart Disease?
With commentary by Nir Barzilai, MD, director of the Institute for Aging Research, Albert Einstein College of Medicine, and Brian Kennedy, PhD, president and CEO of the Buck Institute for Research on Aging. Metformin may influence fundamental aging factors that underlie many age-related conditions, including cancer, heart disease and Alzheimer's, says Nir Barzilai, MD, director of the Institute for Aging Research at Albert Einstein College of Medicine, the Bronx. "Metformin is generic, and it's cheap," Dr. Barzilai says. And accumulating data suggests that ''it interferes with the biology of aging." Aging, he says, is a primary risk factor for not only diabetes but also most of our big killers, such as Alzheimer's, heart disease and cancer. In animal and human studies, metformin has shown promise in slowing the aging process and halting diseases. To study the potential of metformin further, Dr. Barzilai plans to launch a large-scale study, Targeting Aging with METformin (TAME), to look at the effects of metformin compared to placebo. His team has already completed the MILES study, Metformin in Longevity, and are analyzing the results. In that study, they gave some participants metformin, at 1,700 milligrams a day, and others placebo. The aim was to see if the metformin could restore the gene expression profile of an older person with blood sugar problems known as impaired glucose tolerance (but not yet diabetic), to that of a younger person. Dr. Barzilai knows he has critics of his approach. He brushed them off, saying the people who don't see the value of the research ''don't understand the biology of aging and that it can be changed." He doesn't see the research as testing an anti-aging drug. "Aging is not a disease and we don't want it to be a disease," he says. Howe Continue reading >>
We Read This 800-page Report On The State Of Longevity Research So You Dont Have To
We Read This 800-Page Report on the State of Longevity Research So You Dont Have To The longevity field is bustling but still fragmented, and the silver tsunami is coming. That is the takeaway of The Science of Longevity , the behemoth first volume of a four-part series offering a birds-eye view of the longevity industry in 2017. The report, a joint production of the Biogerontology Research Foundation , Deep Knowledge Life Science , Aging Analytics Agency, and Longevity.International , synthesizes the growing array of academic and industry ventures related to aging, healthspan, and everything in between. This is huge, not only in scale but also in ambition. The report, totally worth a read here , will be followed by four additional volumes in 2018, covering topics ranging from the business side of longevity ventures to financial systems to potential tensions between life extension and religion. And thats just the first step. The team hopes to publish updated versions of the report annually, giving scientists, investors, and regulatory agencies an easy way to keep their finger on the longevity pulse. In 2018, aging remains an unnamed adversary in an undeclared war. For all intents and purposes it is mere abstraction in the eyes of regulatory authorities worldwide, the authors write . People often arrive at the field of aging from disparate areas with wildly diverse opinions and strengths. The report compiles these individual efforts at cracking aging into a systematic resourcea periodic table for longevity that clearly lays out emerging trends and promising interventions. The ultimate goal? A global framework serving as a road map to guide the burgeoning industry. With such a framework in hand, academics and industry alike are finally poised to petition the kind of larg Continue reading >>
Anti-aging Human Study On Metformin Wins Fda Approval
News Reports around World Describe Multiple Benefits The media has caught up to the potential health benefits of metformin, something our long-term supporters discovered long ago. What caught the media’s attention was the FDA’s approval of the first human study to see if metformin can protect against the multiple diseases of aging. Prominent headlines around the world proclaimed: “New Anti-Aging Drug Could Extend Human Life Span to 120 Years” Metformin of course is not a new drug. It was approved in England in 1957 and made available to type II diabetics around the world shortly thereafter. It took the FDA a staggering 37 years to approve it in the United States. Here are some accurate quotes from worldwide news sources: “Although it might seem like science fiction, researchers have already proven that the diabetes drug metformin extends the life of animals, and the Food and Drug Administration in the US has now given the go-ahead for a trial to see if the same effects can be replicated in humans.” “I have been doing research into aging for 25 years and the idea that we would be talking about a clinical trial in humans for an anti-aging drug would have been thought inconceivable…20 years ago aging was a biological mystery. Now we are starting to understand what is going on.” “Scientists think the best candidate for an anti-aging drug is metformin, the world’s most widely used diabetes drug, which costs just 10p [15 cents] a day. Metformin increases the number of oxygen molecules released into a cell, which appears to boost robustness and longevity.” “If we can slow aging in humans, even by just a little bit, it would be monumental. People could be older, and feel young.” “This would be the most important medical intervention in the modern e Continue reading >>
Could A Pill Put The Brakes On Aging?
March 29, 2017 -- The No. 1 risk factor for all the big diseases -- cancer , heart disease , Alzheimer’s -- is aging. But instead of treating the diseases, could a drug treat the aging process itself? That’s the idea behind a growing area of research drawing extensive support from both government and private donors, including millions from Silicon Valley executives like Microsoft co-founder Paul Allen and venture capitalist Peter Thiel. While federal science agency budgets have struggled in the past decade, funding at the National Institute on Aging has risen more than 50% since 2007. Researchers are seeking a drug to push back the most serious consequences of aging -- and keep people healthy, active, and alert years longer, a notion they call “health span.” “I’m not interested in creating a population that lives to be 200, because that would be a problem for the world we live in,” says Corinna Ross, PhD, a biologist at Texas A&M University in San Antonio. “But if we can keep people out of nursing home care and reduce the number of Alzheimer’s and Parkinson’s patients, that would be ideal.” What scientists know about aging has advanced sharply in the past 2 decades as they learn more about what drives the aging process within cells. With the race on to find an anti-aging pill, two of the most promising ones are drugs that already exist: metformin and rapamycin. Doctors have prescribed metformin, the most common drug to treat type 2 diabetes , for about 60 years. But it’s received new attention as a possible anti-aging drug after researchers in Britain found that people with diabetes who took it outlived some of their peers who did not have the disease by 15%. “They compared them to a whole bunch of people who were matched for weight and smokin Continue reading >>
American Federation For Aging Research : News
AFAR Grantee, Awardee, and Board member in the News: Bonkowski, Guarente, Mitchell, and Sinclair research on sirutins and longevity published in Cell On March 22, 2018, Cell published research on sirutins and longevity co-authored by several AFAR experts: 2011 Ellison Medical Foundation/ AFAR Postdoctoral Fellows and 2007 Eweson Series Lecturer Michael Bonkowski, Ph.D. 2015 Irving S. Wright Award of Distinction winner Leonard Guarente, Ph.D. 2009 Glenn Foundation for Medical Research and AFAR Grant for Junior Faculty recipient James Mitchell, Ph.D.; and 2000 Glenn Foundation for Medical Research and AFAR Grants for Junior Faculty recipient and Board member David Sinclair, Ph.D. In Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging, the researchers Grantee in the News: Rozalyn Anderson Insights in HealthDay on Calorie Restriction and Longevity On March 22, 2018, Healthday highlighted the insights of 2016 Glenn/AFAR Breakthroughs in Gerontology (BIG) Award winner Rozalyn Anderson, Ph.D. Want to Live Longer? Eating a Little Less Might Do the Trick, explores a new study tested on humans showing that caloric restriction significantly decreases metabolism and may lead to a longer lifespan. The study involved 34 healthy people following a calorie restricted diet for 2 years. Cited as an AFAR expert, Anderson noted the similarities between the study done on humans and her research on caloric restriction on monkeys. So much of what they Awardee in the News: Valter Longos research on Health Benefits of Fasting in Business Insider On March 19, 2018, Business Insider highlighted 2013 Vincent Cristofalo Rising Star Award in Aging Research recipient Valter D. Longo, Ph.D. The article, The amazing ways intermittent fasting affects your bod Continue reading >>
Is There Any Truth To Anti-aging Schemes? | Popular Science
By Andrew Zaleski 2018-06-12T09:30:00-04:00 On a Thursday evening in late January, the faithful gather. They trickle into the Church of Perpetual Life, about an hours drive north of Miami, until a throng of around 100 people cram around tables lining the first-floor hall of this renovated house of worship. Along one wall is a display of reading material: pamphlets on heart disease , flyers itemizing the additives in Cheez-Its and their detrimental health effects, a handbill about the Ms. Senior Florida pageant. On the other side of the room, theres a snack buffet with beans, broccoli, carrots, cubed cheese, sliced meats, and olives. Its easy to pick out the regulars, who mingle clutching biology textbooks or readily shaking hands. Many of them pause to greet the diminutive man who is their host: Bill Faloon. Clean-shaven and youthfully slim in a dark suit, with jet-black hair and a formidably bridged nose, he is the churchs founder. Just yesterday, he laid out its gospel to me, saying, Were talking about immortality. His followers, he says, are people trying to live as long as possible, maybe even forever. At 63, Faloon is old enough to remember when such talk labeled you a kook or charlatan. In the late 1970s, he co-founded the Life Extension Foundation, a nonprofit promoting the notion that people dont need to dieand later started a business to sell them the supplements and lab tests to help make that dream real. Nowadays he also distributes a magazine to 300,000 people nationwide and invites speakers to monthly gatherings at the church, billed as a science-based, nondenominational meeting place where supporters learn about the latest developments in the battle against aging. Their faith is in human technologies that might one day end involuntary death. After an hour Continue reading >>
The Mother Of All Clinical Trials, Part I
The Mother of All Clinical Trials, Part I Part I: An Incipient Revolution in Epidemiology There are a great number of promising interventions that might have anti-aging benefits, singly and in combination. There is a testing bottleneck, which means that we dont know what works. By way of contrast, there is a well-documented catalog of life extension interventions in lab worms , but for humans were mostly in the dark. To complicate things further, lab worms are clonal populations, while every human is different, and there are growing indications that many if not most medications work for some people and not others. Horvaths methylation clock is a disruptive technology that could make human testing of longevity interventions ten times faster and 100 times cheaper than it has been in the past.No one is yet doing this kind of testing, but you and I should be advocating vigorously, and volunteering as subjects to help test whatever it is that we are already doing. Let me begin with the punchline, and work backward to build a foundation under the idea. I think we might learn a great deal and push the science of anti-aging medicine forward with a study encompassing about 10,000 people like you and mepeople who are aware of the long-term consequences of their diet, exercise, supplements, and medications10,000 people who are trying different combinations of things in a conscious effort to maintain long-term health and extend their lives. We need a standard form for recording our individual habits and a standard measure of progress. Subjects will be required to keep diaries of what they are doing for long-term health (It would be helpful but not necessary that they keep to the same program for a year or two.) send in blood or urine samples at the beginning and end of a year for Continue reading >>
Could Your Diabetes Medication Be The Next Anti-aging Pill?
The subject who is truly loyal to the Chief Magistrate will neither advise nor submit to arbitrary measures. The most common treatment for type 2 diabetes a generic drug called metformin may do a lot more than just regulate insulin levels. Scientists studying its potential as an anti-aging pill say the drug slows the burn rate in living cells in ways that increase longevity. Derived from a plant called French lilac, metformin costs pennies a pill. Studies in animals suggest the drug could delay the onset of chronic diseases, such as cancer and dementia, by targeting the biology of aging, said Dr. Nir Barzilai, director of aging research at Albert Einstein College of Medicine in New York. You give it to nematodes [microscopic worms], you give it to rats, to mice they all live longer. But worms and rodents are short-lived creatures. Could metformin have the same effect in humans? Barzilai has teamed up with colleagues from more than a dozen research centres across North America to answer that question. Theyre gearing up for a US$77-million clinical trial called TAME, short for targeting aging with metformin, and plan to start recruiting 3,000 adults aged 65 to 80 in the next year or so. Barzilai predicts that people on the drug will have less disease. In observational studies , he pointed out, patients taking metformin for diabetes have shown lower rates of cancer, dementia and cardiovascular disease. But observational studies of patients taking a drug for a specific disease are very hard to interpret, said Dr. Judy Wong, an associate professor of pharmaceutical sciences at the University of British Columbia. After all, one of the first things a physician tells a patient with type 2 diabetes is you have to change your lifestyle, said Wong, who studies how cellular change Continue reading >>
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