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METFORMINE
A Drug That Millions Take For Diabetes May Fight
The Fundamental Causes Of Aging

26 August 2015, By Andrea Alfano Tech Times
[Lien / www.techtimes.com]

US FDA donne son accord pour l'essai chez l'homme de la metformine
en tant que médicament anti-âge

Les résultats de modèles animaux et d'études in vitro suggèrent qu'en plus de ses effets sur le métabolisme du glucose (anti-diabétique), la metformine pourrait agir sur les processus métaboliques et cellulaires associés au développement de troubles liés à l'âge tels que l'inflammation, les dommages oxydatifs, l'autophagie diminuée, la sénescence cellulaire et l'apoptose .
Ainsi les patiets traités par la metformine ont 30% de cancers en moins pour presque tous les cancers sauf peut-être le cancer de la prostate. Pour le déclin cognitif il ya moins d'études mais la metformine pourrait avoir un effet préventif. En outre, il ya une étude qui suggère que les patients diabétiques mis sous metformine (qui sont généralement plus obèses et plus malades que les personnes sans diabète) vivent "paradoxalement " plus longtemps que les personnes sans diabète " et bien sur sans metformine....

Revoir : La metformine reste le meilleur traitement du diabète type II. [Lire]

Today, the only drugs marketed as "anti-aging" are the phony ones seen in spammy Internet ads. However, some doctors and scientists argue that some of the drugs already in use today treat age-related diseases so well because they are actually targeting the fundamental biological processes that cause aging.

Metformin, a diabetes drug for which 48 million prescriptions were filled in 2010 alone, is one of those drugs. Scientists studying the biology of aging, with support from the American Federation for Aging Research (AFAR), are planning a clinical trial to test metformin as a drug that targets aging so that the U.S. Food and Drug Administration might recognize aging as an indication for drug use for the first time. This is not a study aimed at finding a drug that will allow humans to achieve immortality or even necessarily increase lifespan significantly. Instead, the focus is on increasing healthspan — the amount of time for which a person lives healthily, free of debilitating age-related diseases — so that it might take 70 years to feel as run down as you might have otherwise felt by age 50.

They call it the TAME study, short for Targeting Aging with MEtformin. This past June, they got the "green light" from the FDA — meaning that if they see the results they expect based on observations from the past 60 or so years of using metformin as a diabetes drug, the FDA plans to open up a whole new world of pharmaceuticals by recognizing aging itself as a targetable cause of disease.

"People on metformin get 30 percent less cancers, almost every cancer except maybe prostate cancer.
There are fewer studies, but there is a signal that metformin prevents cognitive decline. Additionally, there is a study that suggests that people on metformin who, when they start taking metformin, are more obese and sicker than people without diabetes, they outlive people without diabetes," Nir Barzilai, director of the Albert Einstein College of Medicine's Institute for Aging Research and co-leader of the TAME study, tells Tech Times.


Right now, there are drugs designed specifically for Alzheimer's disease or for cancer or for cardiovascular disease or any other particular type of age-related disease because the FDA recognizes these diseases as valid and separate targets for pharmaceuticals. The question that the TAME trial aims to answer is, can a drug target multiple age-related diseases at once?

"The number one purpose is the idea that we have a drug that we can use in humans that can delay or prevent aging. But the second goal, which is in a way more important if the study works, is to convince the FDA that aging can be a target," Barzilai explains.

The biology of aging is a relatively new field of scientific research, but evidence is mounting that many of the outcomes we associate with aging are caused by so-called fundamental aging processes in our bodies. These processes include those by which our key molecules such as DNA become dysfunctional and chronic inflammation sets in without any infection by bacteria or viruses. They also include the processes by which cells begin to die more destructively and the stem and progenitor cells that once gave rise to new cells become dysfunctional.

All of these processes are interconnected and their interactions are complex. However, the more scientists learn about them, the more it appears that these core processes underlie a variety of age-related diseases. It is plausible, even, that this is the reason that certain drugs that are already widely used have the "side effect" of slowing the onset of age-related diseases that they were not initially intended to treat.

"I think we're already giving people drugs for aging. I think that's what we're doing with metformin," Brian Kennedy, who is not involved with the TAME trial and serves as CEO and professor at the Buck Institute for Research on Aging, tells Tech Times. "The reason it works is that it affects the biggest risk factor for diabetes, which happens to be a big risk factor for age-related disease. The same argument can be made for baby aspirin."

Toward the end of life, many people essentially end up trading one age-related disease for another. They may receive a stent in their heart, for example, only to die of Alzheimer's a few years later.

"We know that people in their 80s and 90s, if they get one age-related disease, the time for them to get to the second one is roughly two years, and then the third one might be even faster than that," Barzilai says.

Aging researchers such as Barzilai are calling for a change in perspective. Instead of playing whack-a-mole, they argue, let's just start dismantling the whole underground network from which they keep popping up.

Barzilai and his colleagues who are collaborating with him on the TAME study have not chosen to study metformin as a drug that targets aging because they think it is the best at it. They chose it because it is cheap, it is generic and it is relatively safe as far as pharmaceuticals go. That means that this trial does not have to be concerned with proving that metformin should be approved as a drug fit for use in humans. The aim is to pave the way for new pharmaceuticals that specifically target aging and are likely to do so even more effectively by proving that a single drug can slow the onset of a variety of age-related diseases.

The first major way the TAME study would accomplish this is by making it financially feasible to create better drugs to target aging. So far, pharmaceutical companies have had little incentive to explore drugs that target aging because insurance companies would not pay for them. If the FDA approves aging as an indication for drug use, that means insurance companies would pay for such drugs.

The second key benefit of the TAME trial is that, if successful, pharmaceutical companies will have a framework for performing a clinical trial to prove their drug targets aging. Since aging is something that of course occurs over a very long period of time, this is not an easy task. However, Barzilai and his colleagues have come up with a clever strategy.

They plan to enroll approximately 3,000 elderly people between the ages of 70 and 80 who have suffered from one or two age-related conditions, including ischemic heart disease, stroke, cancer and mild cognitive impairment. Anyone with diabetes will be excluded since this is the condition that metformin is already intended to treat. Some of the participants will begin taking metformin regularly for the next five years, and then the researchers will measure how long it takes them to develop additional age-related conditions. If this period of time is longer in the people taking metformin compared with those who were given a placebo instead, this suggests that metformin has delayed the onset of age-related disease.

Even if this is exactly what happens, chances are low that the FDA will call metformin or any other drug an "anti-aging" drug, Barzilai explains. It's more likely that they will put it in terms of the "comorbidities of aging," which basically means all of the negative health effects strongly linked to aging.

Regardless of what you call it, looking at health care from this perspective has potential to cut costs in a radical way. On the patient's end, not surprisingly, health care costs are far higher for people over the age of 65 than they are for younger people, precisely because of the accumulation of age-related disease. However, there ar

e financial incentives to this approach on the pharmaceutical company's end, too. "For each indication on a drug label — for example, heart attacks or stroke or Alzheimer's disease — each of those indications costs anywhere between one and five million dollars to do the clinical trials. If you can say that you can target many of them together, then you're collapsing the cost of development," James Kirkland, director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic and board member for AFAR, tells Tech Times. "The advantage of that is it would increase the enthusiasm of the pharmaceutical industry to look at drugs that target fundamental aging processes because it would save tremendously on their drug development costs and risks if they can get several indications registered for the same price as having a single registration."

It's too early to say how much metformin or any other drug can delay the effects of aging at this point, or even exactly when the results of the TAME study will be in. Only in recent years have scientists been able to achieve repeatable, pre-clinical data to show that they can target aging in animals. The way Barzilai sees it, "the perfect storm is happening now." However, as a scientist who studies some of the oldest, and arguably wisest, people alive — centenarians — he knows that he needs to be patient.

"This realization is grassroots," he says. "It takes time."



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. [Lire]

Dr. Nir Barzilai on the TAME Study
Healthspan Campaign partner the Albert Einstein College of Medicine was recently featured in The Wall Street Journal about a groundbreaking new study called Targeting/Taming Aging With Metformin, or TAME. We had the chance to speak with Nir Barzilai, M.D., director, Institute for Aging Research, Einstein College of Medicine, and, scientific co-director, the American Federation for Aging Research, to learn more about it. [Lire]

US FDA gives OK for human trial of metformin as anti-ageing drug to prolong life until 120 years [Lire]

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