The Popular Science Media Fails to Distinguish Between Potentially High Yield and Probably Low Yield Treatments for Aging

It is of great importance to distinguish, where we can, between promising and poor approaches to the treatment of aging. If only poor approaches are developed, then we'll age, suffer, and die on much the same schedule as our grandparents. In the article here, metformin and senolytics are crammed together side by side, as though the same thing. They are very much not the same thing.

Metformin is almost certainly a poor approach to the treatment of aging. The animal data is terrible, while the human data shows only a modest effect size. Senolytics are most likely a promising approach. The animal data is amazing: robust, reliable rejuvenation and reversal of many currently untreatable age-related diseases via any approach that removes a third or more of the senescent cells that linger in old tissues. The degree to which this is going to do great things in people remains to be determined. But it is fair to wager that it will be a good deal better than the results to date from metformin. If we're going to spend extensive time and funding on something, why the obviously worse option? Why aim so low?

In recent years, many experts in the aging field have come to believe that certain medications acting at the cellular and metabolic level can slow aging by staving off its most striking effects - frailty and ­age-related diseases, for example - and extend healthy life in doing so. Now they are setting out to prove it. "We're not about the fountain of youth," says Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine. "That's taking an old person and making him young. What we are saying is that we can delay aging."

Drugs with the ability to postpone or prevent the onset of debilitating diseases could lead to additional healthier years, enhancing longevity and providing enormous societal benefits, experts say. Leading the list of candidates is metformin, a longtime treatment for type 2 diabetes, and rapamycin, a chemotherapy agent and immunosuppressant. Scientists also are studying a class of compounds known as senolytics, which attack "senescent" cells in the body that tend to proliferate with age. Senescent cells damage healthy cells around them, contributing to multiple age-related diseases.

But such drugs could face a daunting challenge, since aging is not considered a disease. This means the Food and Drug Administration is unlikely to approve a drug for its anti-aging effects, or as a new use for a licensed drug. Also, pharmaceutical companies probably wouldn't be inclined to develop drugs for that purpose only. Scientists hope to circumvent that hurdle by conducting a study - in this case, with metformin - to test whether it can prevent or delay three age-related diseases - dementia, heart disease and cancer - and, in doing so, extend life.

At least one study had heightened their interest in the drug as possibly life-extending after researchers noticed that diabetics who took the drug outlived non-diabetics who did not. Moreover, metformin had shown an effect in separate studies against each of the three diseases, prompting the researchers to try to put all the pieces together in one large randomized controlled clinical trial. The result is a proposed six-year clinical trial, known as Targeting Aging With Metformin (TAME), which will recruit 3,000 subjects ages 65 to 79 at 14 research sites. In testing whether metformin can prevent or delay the three diseases, researchers also hope to learn whether this results in those taking metformin outliving those not taking the drug, thus extending healthy life. (One reason for choosing metformin was because of its long track record, safety, and inexpensive cost.)

"The goal is not to help people live forever, but help them stay healthy longer," says Steven Austad, who chairs the biology department at the University of Alabama at Birmingham and is senior scientific director of the American Federation for Aging Research. "But the fringe benefit is that you live longer."



Sorry - senolytics had their chance and blew it via the Unity / UBX-0101 / OA fiasco

It will take a lot of work to convince the press that there is "meat" there to get excited again until the clinical data is real

Metformin has a safe track record over decades and has performed well in humans for decades - there is no spin - makes for a good story and Nir is a credible face

Posted by: barry demarco at March 16th, 2021 10:00 AM

Senolytics are the only viable anti aging treatment we have so far. One study by unity has discredited absolutely nothing. The field of senolytics continues to grow and you can easily take some senolytics now on your own. You keep pounding metformin and I will intelligently use senolytics and effective treatments.

Posted by: David at March 16th, 2021 1:00 PM

There are many different senolytics targeting different senile cells, and not all of them were tested in humans. Some of them may slow down or partly reverse aging process.
However, partial rejuvenation may not contribute to life extension beyond maximum (120 years)
This is the HYPOTHESIS that must be experimentally proven in Humans: that rejuvenation also has the effect of life extension __ it would be a break through when it is proven.

Posted by: nicholas D. at March 16th, 2021 2:21 PM


You missed my point entirely

The focus here is about the popular press coverage

With the exception of the Unity UBX-0101 trial, which failed, it's all animal data for senolytics at this point - I don't count the folks self-experimening with fisetin, etc. as an equivalence

So you are positioning for media coverage by putting small animal data up against a drug with 60+ years of human exposure

Senolytics will not receive decent coverage again until they prove themselves in the clinic as being a real option for humans

Posted by: barry demarco at March 16th, 2021 4:47 PM

@Nicholas D.:

"This is the HYPOTHESIS that must be experimentally proven in Humans: that rejuvenation also has the effect of life extension __ it would be a break through when it is proven."

That's straightforward. By definition, rejuvenation produces life extension, because aging is defined as the increase in mortality rate with (chronological) age.

Posted by: Antonio at March 16th, 2021 6:29 PM

Let me jump into this flaming discussion. Senolytics are the most promising but not the only candidate.

@nicholas D
It might very well turn out that there senolytics don't increase the max life span. But very likely will increase the health span and probably the average life expectancy. But even if at the end everyone drops dead it would still be a major improvement of the state of the art. If we make to push the life expectancy to 120(with associated reduced and delayed morbidity it would be an immense achievement. And once such an improvement is proven it will get a lot of financing . We need one big win (and UBX is a disappointment and even a setback) to open the floodgates of investing and having dot-com style boom (and associated busts but the research and discoveries will stay)

Posted by: Cuberat at March 16th, 2021 7:35 PM

"the folks self-experimening with fisetin" the fisetin alone is very weak senolytic and it's cell type range in humans still not broad enough to achieve sizable SASP lowering, we "the folks" are using it in combinations now (like fisetin + luteolin + AHCC, or for short F+L+AHCC) or dr Green promoting D+F instead of D+Q, and using lots of calcium/CaAKG and collagen to counter it's side effects.

Posted by: SilverSeeker at March 17th, 2021 6:44 AM

'"The goal is not to help people live forever, but help them stay healthy longer," says Steven Austad, who chairs the biology department at the University of Alabama at Birmingham and is senior scientific director of the American Federation for Aging Research.'

No, jerk, the goal IS to live forever. It's time for longevity scientists to stop LYING about this.

Posted by: Tom Williams at March 18th, 2021 5:06 AM

One step at a time. If we manage to become healthy super centarians then we are almost there...

For now we have only CR to get only a few extra years at great efforts

Posted by: Cuberat at March 18th, 2021 9:33 AM

You are right, the goal IS to live for ever in perfect health and youthfulness.-This is Plan A
True Faith of a Perfectionist.
But not everyone can achieve Plan A. So Plan B Is : Max life span, Max health span, Max youthfulness - achievable by non-perfectionists- the majority of humanity.

Posted by: Nicholas D. at March 19th, 2021 6:15 PM
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