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. 2025 Apr 12;11(1):27.
doi: 10.1038/s41514-025-00217-0.

Relationship between physical activity and DNA methylation-predicted epigenetic clocks

Yanwei You #  1   2 , Yuquan Chen #  3 , Hao Ding #  1   2 , Qiyu Liu #  4 , Rui Wang  1   2 , Kailin Xu  5 , Qingyuan Wang  1   2 , Danijela Gasevic  3   6 , Xindong Ma  7   8
Affiliations

Relationship between physical activity and DNA methylation-predicted epigenetic clocks

Yanwei You et al. NPJ Aging. .

Abstract

This study investigates the relationship between physical activity (PA) levels and DNA methylation (DNAm)-predicted epigenetic clocks in a U.S. population sample (n = 948, mean age 62, 49% female). Eight epigenetic clocks were analyzed, revealing that higher PA levels were significantly associated with younger biological ages across all indicators, with the strongest effects observed for SkinBloodAge and LinAge. Multivariable linear regression models, adjusted for sociodemographic and lifestyle factors, highlighted the potential of PA to reduce biological ageing. Subgroup analyses indicated that these associations were more pronounced among non-Hispanic whites, individuals with a BMI of 25-30, and former smokers, suggesting that the impact of PA varies across different groups. These findings emphasize the role of PA in slowing biological ageing and reducing age-related health risks. Promoting regular PA, especially among older adults and those with higher BMI, could improve well-being and lifespan, highlighting PA as a modifiable factor in healthy ageing and age-related disease prevention.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Research Summary and Study Design.
Fig. 2
Fig. 2. Linear associations between physical activity and DNA methylation-predicted chronological and phenotypic age.
A–H Represent relationships between physical activity and different epigenetic clocks, including A HorvathAge, B HannumAge, C SkinBloodAge, D LinAge, E WeidnerAge, F VidalBraloAge, G ZhangAge, and H PhenoAge.
Fig. 3
Fig. 3. Subgroup analysis of associations between physical activity and DNA methylation-predicted chronological and phenotypic age.
A–H Present stratified results for A HorvathAge, B HannumAge, C SkinBloodAge, D LinAge, E WeidnerAge, F VidalBraloAge, G ZhangAge, and H PhenoAge.
Fig. 4
Fig. 4
Flow chart of the study design.
See this image and copyright information in PMC

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