Physical activity lowers mortality and supports healthy aging, but the relationship between the total dose of exercise and epigenetic markers of biological age remained unclear. Research in this area has already accumulated data on how training affects DNA methylation, grip strength, gait, and cellular aging. This study adds to that body of work by being the first to quantify exactly how many MET-hours are needed to slow epigenetic clocks in people without chronic disease.
78 participants (36 men, 42 women) free of cardiovascular, pulmonary, psychiatric, and oncological diseases completed a six-month program of high-intensity interval training three times a week. Total load was expressed in MET-hours (intensity in metabolic equivalents multiplied by duration). Before and after the intervention, researchers measured epigenetic age using several DNA methylation-based clocks, body composition by DEXA, echocardiographic parameters, lipid profile, cognitive function, and gut microbiome composition. Dose-response relationships were analyzed using robust regression adjusted for sex and chronological age.
A greater volume of exercise in MET-hours was associated with a more pronounced reduction in epigenetic age acceleration on the Robust PhenoAge and Robust GrimAge clocks. In the unadjusted model, reducing Robust PhenoAge acceleration by one year required about 109.7 MET-hours over six months, while Robust GrimAge required about 202 MET-hours. With no physical activity, the predicted age acceleration was positive, indicating the expected aging that occurs without exercise. To achieve a one-year slowdown, a person with no exercise load would need roughly 255 MET-hours (PhenoAge) or 378 MET-hours (GrimAge) over six months, which is comparable to WHO recommendations (260-520 MET-hours).
This work stands out from neighboring studies because it establishes a quantitative dose-response link between total exercise load and epigenetic aging in healthy adults, not just in athletes or patients. It is the first test of whether even moderate exercise volumes, comparable to WHO recommendations, can slow the molecular clocks of aging. The resulting MET-hour thresholds provide a benchmark for future intervention studies and personalized recommendations.
The field could move toward randomized controlled trials with different exercise doses to confirm causality. It would be promising to study how individual characteristics (sex, age, baseline fitness) modify the response of epigenetic clocks to exercise. It would also be interesting to determine which molecular mechanisms mediate this link, including the role of TGF-α, TIMP1, and changes in the microbiome.
The results will influence gerontology, sports medicine, preventive cardiology, and nutrition science by providing quantitative benchmarks for prescribing physical activity to slow biological aging.
Conduct a randomized controlled trial with groups assigned to different exercise intensities and volumes to confirm causality. Study how long the slowdown in epigenetic aging persists after training stops and how it relates to long-term health outcomes.
This work directly addresses an unresolved problem in gerontology: which modifiable lifestyle factors, and at what dose, can slow biological aging. It links epigenetic clocks to functional and metabolic changes, but leaves open the question of whether the slowing of the clocks causes better health or merely reflects it.
Elite athletes, such as Tour de France cyclists, can accumulate 250-400 MET-hours per week, which is 29-47 times the load needed to slow epigenetic age by one year under the most conservative model.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.