Longer Life in a Pill May Already Be Available at Your Local Drug Store

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To most of the scientific community, “anti-aging” is a dirty word.

A medical field historically associated with charlatans and quacks, scientists have strictly restricted the quest for a “longevity pill” to basic research. The paradigm is simple and one-toned: working on model organisms by manipulating different genes and proteins, scientists slowly tease out the molecular mechanisms that lead to — and reverse — signs of aging, with no guarantee that they’ll work in humans.

longer-life-in-a-pill-41But it’s been a fruitful search: multiple drug candidates, many already on the market for immune or psychiatric disorders, have consistently delayed age-associated diseases and stretched the lifespan of fruit flies, roundworms and mice. Yet human trials have been far beyond reach — without the FDA acknowledging “aging” as a legitimate target for drug development, researchers have had no way of pitching clinical trials to the regulatory agency.

Until now.

This year, the FDA green lighted an audacious proposal that seeks to test in 3,000 volunteers a drug that — based on animal studies — could extend human lifespan by up to 40 percent and decrease chances of getting age-related diseases. The double-blind, multi-centered trial, Targeting Aging with Metformin (TAME), is the first that pushes aging as a bona fide disease — one that may eventually be tamed with drugs.

“We think this is a groundbreaking, perhaps paradigm-shifting trial,” said Dr. Steven Austad, scientific director of the American Federation for Aging Research (AFAR).

A Sea Change

Without a doubt, TAME is an odd one in the realm of clinical trials. Spearheaded by Dr. Nil Barzilai, an ebullient scientist based at the Albert Einstein College of Medicine, TAME receives no support from the pharmaceutical industry. The brainchild of a team made up solely of academics, TAME is sponsored by the nonprofit organization AFAR.

Even more of a head scratcher is this: if the drug were to work in humans — making it the first scientifically proven longevity pill, an elixir worth billions — none of the team members stand to make any money. This is because metformin, the star of the trial, is a generic diabetes drug that costs only a few cents a dose.

It’s not about the money; it’s something far bigger.

What we’re talking about here is an idea that fundamentally changes how we look at aging and disease, said Dr. S. Jay Olshansky, a biodemographer at the University of Illinois and TAME team member.

The idea is this: rather than tackling the top medical killers — cancer, cardiovascular disease, dementia — individually, we should instead focus on slowing or reversing the single most prominent risk factor associated with all those diseases — age.

It may be as close to a silver bullet as we’ll get.

The Drivers of Aging

TAME is built on decades of basic research on aging, mostly conducted in short-lived model organisms such as fruit flies, nematode worms and mice. By individually tweaking genes and measuring the resulting effects on healthspan and lifespan, scientists gradually teased out individual molecular pathways that drive aging forward.

longer-life-in-a-pill-7Within the last few years, the field has built a solid theoretical framework of the aging process. Endearingly known as the “major pillars of aging,” the framework includes pathways related to metabolism, stress response, inflammation, stem cell quality and proteomic homeostasis — that is, the body’s ability to keep groups of proteins functioning in harmony.

Yet scientists have not yet teased out the so-called “master regulators,” or central cross points that bridge the different pathways and drive aging forward.

Some of us think that the brain is the central regulator, that inflammatory processes in the hypothalamus are sufficient to drive aging of the body, said Dr. Dongsheng Cai, a neuroscientist at the Albert Einstein College of Medicine.

Our current anti-aging apothecary contains antidepressants, said Dr. Michael Petrascheck, a researcher at the Scripps Institute, to Singularity Hub. And we think those drugs act on the brain, which in turn regulates gene expression in the body to increase stress resistance and increase lifespan.

Others, in contrast, think pro-aging factors in the blood drive brain aging. Last year, a series of groundbreaking studies laid bare the rejuvenating effects of young blood. When researchers diluted the blood of an old mouse by infusing it with blood from a young mouse, the old mouse’s brain, blood vessels and muscles all reverted back to a younger state.

Although master regulators remain elusive, research has uncovered an impressive list of drug candidates. Metformin, TAME’s test drug, sits solidly at the top of that list.

It’s a truly ancient drug. Widely used in humans since the Middle Ages, metformin reduces blood sugar and works on multiple pathways involved in cell growth, inflammation and metabolism — all of which constitute the major pillars of aging.

Epidemiological studies suggest that metformin reduces the risk of cancer and dementia. What’s more, a large 2014 study of 78,000 people showed that on average, people with Type 2 diabetes who take the drug live longer than those of the same age who don’t.

Metformin seems to fit the bill of a longevity drug. But it was the chemical’s two other perks that made it a winner to the TAME team.

First, it’s very safe. When taken as prescribed, the drug has few side effects, and those that do occur are well documented.

Second, and perhaps the kicker, is that in addition to extending lifespan, it also extends healthspan — the number of years that an organism remains healthy, even in old age.

Our goal is not to extend life per se, explained Olshansky. In fact, that was the basis of our proposal to the FDA, he laughed.

Healthspan, Not Lifespan

TAME is based on a promising — if surprising — result repeatedly found in multiple organisms: increases in lifespan have often been associated with increased healthspan. That is, with some manipulations such as caloric restriction, not only have the animals lived longer, they also stayed mentally sharp and able-bodied in those extended years.

If this holds in humans, it could fundamentally change our health care system, said Olshansky.

In many people’s minds aging is not a disease, it’s simply humanity, said Barzilai. So instead of pitching a drug trial that targets aging to the FDA, we proposed to look at comorbidities — that is, chronic diseases that sharply rise in incidence as people age.

longer-life-in-a-pill-8The goal is to see whether metformin delays the onset of age-related comorbidities. This strategy, part of a concept called the “longevity dividend,” was first proposed by Olshanky and colleagues back in 2006. The concept argues that slowing the process of aging has significant benefits in terms of health and wealth for individuals and the health care economy as a whole.

In a 2013 paper published in Health Affairs, Olshansky broke down the numbers. Based on animal models, even a small delay in aging could raise life expectancy by an additional 2.2 years, most of which is spent in good health. Over fifty years, the economic value of delaying aging is estimated to be $7.1 trillion. In contrast, targeting comorbidities separately — for example, heart disease and cancer —would end in diminishing improvements in health by 2060, mainly due to competing risks, argues Olshansky. It’s basically changing one disease for another.

“We’re not arguing — and we’ve never argued — that we’re trying to achieve life extension,” said Olshansky in an interview with Science News. “We’ll probably live a little longer if we succeed, but that’s not the goal. The goal is the extension of the period of healthy life.”

Opened Doors

If TAME goes well, it’s only the first step towards battling aging in humans.

In addition to testing the effects of metformin, the TAME team also plans to take muscle and fat biopsies of volunteers before and after taking the drug. By using a big-data technique called RNA deep sequencing, which looks at what genes are expressed at what levels, the team hopes to identify biological “fingerprints” for aging.

Gene expression is like an orchestra — some groups of genes always turn on together, others always shut off. With age, however, gene expression patterns slowly drift out of whack, a phenomenon that researchers call “transcriptional drift.”

Reversing transcriptional drift is a great readout when trying to test the effects of new longevity drug candidates, said Petrascheck. In a study published this week, Petrascheck identified miaserin, an antidepressant already on the market, as a new type of “longevity pill” that extends young adulthood in worms without affecting later years.

Without a doubt, data from TAME will be incredibly valuable for judging other anti-aging drug candidates.

Regardless of how the trial turns out, the TAME team is optimistic.

The main reason we set out on this is to convince the FDA to approve aging as an indication, so that it can be a target for future trials with even better medications said Barzilai.

We got it, he said.

Image Credit: Shutterstock.com

Shelly Fan

Shelly Xuelai Fan is a neuroscientist at the University of California, San Francisco, where she studies ways to make old brains young again. In addition to research, she's also an avid science writer with an insatiable obsession with biotech, AI and all things neuro. She spends her spare time kayaking, bike camping and getting lost in the woods.

Discussion — 13 Responses

  • Facebook - richard.r.tryon December 6, 2015 on 12:07 pm

    I read this a.m. that by 2050 the experts on population predict an added 2.4 billion more mouths to feed. Yes, I can rotate plants on towers 100′ tall and put 10,000 of them in 200 acres. Co-ordinating raw materials to get seedlings in place and harvest to be floated away on the same channels of water that bring the seedlings and fish fingerlings to make the fertilizer needed for plants to grow, is hard to do, but possible to feed all.

    But, now you tell me must also produce that much more organic small fruits and veggies to let the increased population also live longer! Who says we need so many of our specie? Is it only because consumerism is driving the economy, and our species can’t survive like others by consuming only what we need and have far fewer things that we want?

    • Quantium Facebook - richard.r.tryon December 6, 2015 on 2:18 pm

      So what is your Final Solution? Line up elderly people and shoot them? Surely not. But withholding treatment for ageing is no different in its result. I think that “murder by neglect” has meaning in law.

      No, there is a simple solution, and it comes naturally. Have fewer babies.

      It has been observed that the more affluent a society becomes, its population do have fewer babies. In fact this is now being seen as a problem in that the indigenous population of developed countries are reaching pensionable age at a time when there are fewer young people to replace them. Pensions are becoming financially unviable.

      The answer is to abolish pensions! This can’t be achieved if elderly people are too enfeebled in body and mind to perform useful work. Abolish ageing, and it can be done.

      Accident becomes the only form of death. The average age of death becomes about 600 years statistically, although this could go up if people start behaving more cautiously.

      The problem with elderly people is not that they exist, but most of them depend on state pensions. Insurance funded pensions are a form of state pension when the premiums are compulsory by law. If the insurance companies fail, which they may, then the state would have to pick up on the pensions — unless the pensioners were so invigorated as a consequence of using the successors of metformin they could again work for a living. Even now, many pensioners are having to take on part time work to supplement a pension made inadequate by inflation.

    • benwade Facebook - richard.r.tryon December 13, 2015 on 9:58 am

      I read your post. I could respond with some platitude that made reference to the sanctity of human life, or the fact that the only thing that has any real value is life, or maybe that a society of older, but still active and healthy people, would be one with less war and greater respect for the earth. All those things are true, but the real reason is that as a species we are going to colonize our solar system at least, if not the stars. Only the short-sighted would fail to realize that as we work incrementally to increase human lifespan and defeat disease, we are also working toward realizing the beauty, majesty and grandeur of the human race.

    • DevilDocNowCiv Facebook - richard.r.tryon December 14, 2015 on 1:21 pm

      rich,

      That’s only an issue if and when we become a world state. Now and for the foreseeable near future, the US, Singapore, China, Japan, the EU, and many other countries should be able to help less competent countries feed their hungry. And please consider that current developing country incompetence in terms of keeping thier people fed may, and I hope will be a past historical note by a hopefully not to distant “then.”

      Why assume that as we “tech up” worldwide, and many more of the developing world has family educated to modern standards are aware of modern issues, they’ll just shrug their shoulders and give up? As the developed world advances, the concern you implicitly show for the worlds poor will be accompanied by concern from myself and many others. At that future date, your imagined high rise farms will only be one of many options.

      You and I both, if we still live, will want to help. So will many others. Fear not that future, my friend, and think not that we have to kill our offspring, so to speak, to make room for the future offspring in other countries.

  • Sharley Peron December 6, 2015 on 3:03 pm

    Great news! It’s difficult see clearly the cost of illness and the chain effects of a longer healthy life, anyway, world is changing too fast and if it’s on a healthy way, it’s all right.

  • ega December 6, 2015 on 7:21 pm

    Metformin extended the life span of a round worm 40%

    There are hundeds of ways you can extend the life of such a short lived animal (2-3 weeks) There is no basis at all to think we would get the same effect/percentage in humans.

    Metformin may have some effect, but don’t expect three decades.

    • benwade ega December 13, 2015 on 9:59 am

      You’re absolutely right. I would expect to see three months at most, and then only as viewed through a statistical lens.

  • Robert Quinn December 7, 2015 on 7:26 am
  • dobermanmacleod December 9, 2015 on 10:25 pm

    I could cite several others too. I really think that the main battle against aging is psychological, in the sense that our society must change the paradigm of aging from inevitable to curable. Stupid (and religious) people are literally endangering my life by their blind acceptance of aging as “natural.”

    http://www.kurzweilai.net/drugs-that-dramatically-increase-healthy-lifespan-discovered-by-scripps-research-mayo-clinic?utm_source=KurzweilAI+Weekly+Newsletter&utm_campaign=d710329921-UA-946742-1&utm_medium=email&utm_term=0_147a5a48c1-d710329921-282163041

    “A research team from The Scripps Research Institute (TSRI), Mayo Clinic and other institutions has identified a new class of drugs that in animal models dramatically slows the aging process, alleviating symptoms of frailty, improving cardiac function, and extending a healthy lifespan.

    They found two drugs — the cancer drug dasatinib (sold under the trade name Sprycel) and quercetin, a natural compound found in many fruits, vegetables, leaves and grains and also sold as a supplement that acts as an antihistamine and anti-inflammatory — can kill senescent cells. These are cells that have stopped dividing and accumulate with age, accelerating the aging process.

    The scientists coined the term “senolytics” for this new class of drugs.”

    • benwade dobermanmacleod December 13, 2015 on 10:06 am

      I would be willing to bet that we are already optimized for longevity in terms of senescent cell life. Getting rid of senescent cells may improve short-term life quality and reduce inflammation, but I’d bet there would be a large long-term cost due to what you might call cellular-penia. We are constantly accumulating mutations. We are obviously lacking some cellular repair machinery that we lost when mammals and other animals passed through the Cretaceous–Paleogene (K–Pg) extinction event

  • Dennis Mark Zabala February 6, 2016 on 4:16 pm

    Metformin reverses aging. The FDA should work on access to metformin without having to be sick. I should be able to buy the metformin in the usa which costs 5 cents a day as a preventative measure instead of requiring a doctor’s prescription for all of us!

  • SweetDoug February 20, 2016 on 7:29 am




    Saturday, February 20, 2016

    Not a peep about this in the news.

    Wonder if this is going to be yet another amazing discovery we hear about, hailed as having so much potential, and then?

    “Pffffttt!” Gone.

    What do you really think the world would look like with all those extra, unemployed people, with no money, as the pensions are broke?

    •∆•
    V-V

    • Quantium SweetDoug February 20, 2016 on 8:07 am

      If death by aging was abolished, then so would pensions be abolished. The transition may be interesting, though. Saving and investment have always been possible, although socialists generally don’t like it, regarding it as hoarding money.

      Quercetin has been available as a supplement for a while. It is hardly news, although anything that may provide scientifically rigorous proof of its efficacy could be I suppose. Also I would imagine that anyone whose existing income streams and investment in education could be adversely affected by lots of people successfully using these products may object.