A Yale-led analysis of more than 50 clinical studies has found that diet, exercise and a handful of prescription drugs measurably slow a key marker of biological aging — while the over-the-counter supplements many people take for the same purpose showed little to no effect.
The study, led by researchers at the Yale School of Medicine and published in Nature Medicine, systematically compared more than 110 DNA-methylation "clocks" — lab tests that estimate a person's biological, rather than chronological, age — across 51 human intervention trials. It's one of the largest efforts yet to test, head to head, which popular anti-aging strategies actually move the needle on these biomarkers and which don't.
Combined healthy eating and exercise consistently lowered participants' epigenetic age, the researchers found, and the effect held up whether the diet in question was Mediterranean, low-carb or low-fat — suggesting the benefit comes from the general pattern of eating well and moving more, not any single diet plan. Prescription drugs produced the largest measured decreases of any category, with metformin, semaglutide (the active ingredient in Ozempic and Wegovy) and anti-TNF anti-inflammatory therapies among those linked to slower aging by the clocks. Supplements and certain medical procedures, by contrast, showed little or no measurable effect.
"For the first time we've shown that certain therapies have measurable impacts," said Raghav Sehgal, the study's first author and an associate research scientist at Yale. Senior author Albert Higgins-Chen, an assistant professor of psychiatry at the medical school, cautioned that a lower reading on an aging clock is not the same as proof of a longer, healthier life: "the true meaning of that change must be fully understood," he said, adding that the more important question is "what does the change mean for our long-term risk of age-related disease and functional decline?"
Why a lower number isn't the whole story
That caveat matters because several of the trials included in the analysis studied people who were already sick, and the researchers found that biomarkers shifted more in those disease populations than in healthy volunteers — raising the possibility that some of the apparent "anti-aging" effect reflects improvement in an underlying illness rather than aging itself. The Yale team also found that newer-generation clocks outperformed older ones, and that one once-promising category, senolytic drugs designed to clear out aging cells, did not hold up well under the broader analysis.
The paper, first published in late August, has continued to circulate in health coverage this week as a practical reference for an increasingly crowded longevity industry. The authors say the next step is validating which biomarker changes actually translate into fewer age-related diseases and longer healthy lifespans — something this analysis, despite its scale, cannot yet answer on its own.
