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."