Physical activity and biological age measured by DNA methylation clocks: a systematic review and meta-analysis.
Level 4 - case-series / case-control
Systematic review and meta-analysis based primarily on cross-sectional observational studies
PubMed 42068988 · doi:10.1016/j.lanhl.2026.100835
What was done
Authors conducted a systematic review and random-effects meta-analysis across six databases (Embase, Cochrane Central, PubMed, Ovid, Scopus, Web of Science) from 2011 to June 2025. They included peer-reviewed human studies with adult populations (mean/median age ≥18) examining associations between physical activity and DNA methylation (DNAm) age, epigenetic age acceleration (EAA), or epigenetic age deviation. Risk of bias was assessed using an adapted Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool, pooling standardized β coefficients and standard errors.
What was found
The systematic review included 44 studies with 145,465 participants (43.2% female, 56.8% male; mean ages 24.1 to 78.5 years), while 7 cross-sectional studies were pooled in meta-analysis. Each 1 standard deviation (SD) increase in metabolic equivalent of tasks (MET)-minutes per week was significantly associated with a 0.03 SD lower Horvath EAA (β = -0.03 [95% CI -0.05 to -0.01]) and a 0.09 SD lower GrimAge EAA (β = -0.09 [95% CI -0.12 to -0.05]). No statistically significant associations were found for Hannum EAA or PhenoAge EAA.
Why it matters
This review provides quantitative evidence that regular physical activity is linked to slower biological aging as measured by specific first- and second-generation epigenetic clocks (Horvath and GrimAge).
Limits
The meta-analytic effect estimates rely entirely on 7 cross-sectional studies, which prevents causal conclusions. Many individual reviewed studies failed to reach statistical significance, and no association was detected for Hannum or PhenoAge clocks.
Cited by
- supports Physical exercise tends to decrease epigenetic age.
- supports Exercise is associated with a slowing of epigenetic aging.