Which aging-clock results actually move? Diet and exercise shifted them across 51 studies; most supplements did not

Edited by Samael A. Tejada, Founder & Editor-in-Chief

Testing earns trust when it grades the testers. TranslAGE applied one ruler — the same 16 clocks, the same 94 measures — to 51 studies and found the longevity market's hierarchy inverted: fundamentals moved the biology, most supplements did not, and the strongest drug signals came from treating actual disease. It also said, plainly, that none of this yet proves anyone lives longer.

How did TranslAGE compare interventions fairly?

Epigenetic clocks estimate aspects of biological aging from chemical tags on DNA, but different studies used different clocks, making results hard to compare. The Yale-led team built TranslAGE to harmonize them: it gathered 51 longitudinal human intervention studies with blood samples before and after treatment — 3,128 samples in all, most from healthy volunteers — and calculated the same 16 aging clocks and 94 additional DNA methylation measures for every study. Interventions fell into four groups: lifestyle, prescription drugs, over-the-counter supplements, and medical procedures.

What moved the clocks, and what did not?

Lifestyle interventions — diet and exercise combined — produced relatively consistent movement in body-aging measures, with Mediterranean-style, low-carbohydrate and low-fat patterns among the diets represented; the analysis establishes no single best diet. Prescription medicines showed effects too: metformin, semaglutide and TNF-blocking anti-inflammatory drugs all shifted aging measures, with the important context that these were largely patients whose underlying metabolic disease or inflammation was being treated — resolving disease moves methylation markers whether or not aging itself reversed. By contrast, many over-the-counter supplements and certain procedures showed little effect in the available studies.

What can a consumer clock result actually tell you?

Less than the marketing implies, on the authors' own account. Clock movement is not proof of rejuvenation, lifespan extension or disease prevention; the measures still need validation as indicators of meaningful benefit, and studies differing in people, duration and design cannot be treated as a head-to-head contest. What TranslAGE does give a reader is a defensible ordering of effort: interventions with broad, proven health effects — diet quality, exercise, and treating real metabolic disease and inflammation, the same forces that govern mitochondrial function — are the ones that register on the best biological-age measures available, while supplement-first strategies, so far, mostly do not.

Where the evidence stands

• Established: Epigenetic clocks estimate aspects of biological aging from DNA methylation patterns in blood; they do not directly measure lifespan, and clock change is not validated proof of rejuvenation.
• Preliminary: Across 51 human studies and 3,128 samples re-scored on 16 clocks plus 94 methylation measures (TranslAGE, Nature Medicine; reported Oct 29, 2026), combined diet-and-exercise interventions moved aging measures more consistently than most supplements, medicines including metformin, semaglutide and TNF blockers also showed effects mainly in treated patients, and many supplements and procedures showed little effect.
• Absent: Head-to-head proof that any intervention extends human lifespan or healthspan, and validation of epigenetic clocks as stand-alone clinical endpoints.