Physical Activity and Biological Age: What Do DNA Methylation Clocks Show?
Summary ID01-BA-RS-00068
Research Summary
Original Publication
Physical Activity and Biological Age: What Do DNA Methylation Clocks Show?
Journal
The Lancet Healthy Longevity, .
- Category
- 01Biological Age
- Evidence
- Systematic Review and Meta-Analysis
- Summary Type
- Latest
What Was Studied?
Physical activity is well established as an important factor in long-term health. It reduces the risk of premature mortality and many chronic diseases associated with aging.
But whether physically active people also show signs of slower biological aging is a different question.
A 2026 systematic review and meta-analysis published in The Lancet Healthy Longevity examined the relationship between physical activity and biological age measured using DNA methylation clocks.
DNA methylation refers to chemical modifications of DNA that influence how genes are regulated. Patterns of DNA methylation change with age and can be used by epigenetic clocks to estimate different aspects of biological aging.
The researchers systematically searched six major scientific databases for human studies published between January 2011 and June 2025.
They identified 44 eligible studies involving 145,465 participants, including 62,887 women and 82,578 men. Mean participant ages across the studies ranged from 24.1 to 78.5 years.
The review examined associations between physical activity and DNA methylation age, epigenetic age acceleration or epigenetic age deviation.
For the quantitative meta-analysis, sufficiently comparable data were available from seven cross-sectional studies.
The analysis included epigenetic age acceleration measures derived from the Horvath, GrimAge, Hannum and PhenoAge clocks.
The central question was whether higher levels of physical activity were associated with lower epigenetic age acceleration.
Key Findings
Higher physical activity was generally associated with lower DNA methylation age
Across the 44 studies included in the systematic review, higher levels of physical activity were generally associated with lower DNA methylation age.
However, many individual associations were not statistically significant.
This means that the overall direction of the evidence was favourable, but the relationship was not consistent across every study or every epigenetic clock.
Higher physical activity was associated with lower Horvath age acceleration
In the meta-analysis, each one-standard-deviation higher level of physical activity, expressed as metabolic equivalent task-minutes per week, was associated with:
0.03 standard deviations lower Horvath epigenetic age acceleration
β = −0.03; 95% CI −0.05 to −0.01
The association was statistically significant but small.
Importantly, this result should not be interpreted as physical activity making participants a specific number of years biologically younger.
The effect was expressed as a standardised statistical measure, not as years of biological age.
The association was stronger for GrimAge
A larger association was observed for GrimAge.
Each one-standard-deviation higher level of physical activity was associated with:
0.09 standard deviations lower GrimAge epigenetic age acceleration
β = −0.09; 95% CI −0.12 to −0.05
This association was also statistically significant.
GrimAge is an epigenetic measure designed to capture biological information associated with mortality and aging-related health risks.
The finding therefore provides additional evidence linking greater physical activity with a more favourable epigenetic aging profile.
The association was not significant for all epigenetic clocks
No statistically significant associations were found for:
* Hannum epigenetic age acceleration * PhenoAge epigenetic age acceleration
This difference between clocks is important.
DNA methylation clocks are constructed differently and capture different biological information. They should not be assumed to measure exactly the same component of aging.
The results therefore do not support the conclusion that physical activity produces a uniform effect across all measures of epigenetic biological age.
The study shows an association, not proof of causation
The strongest limitation is the nature of the available evidence.
The seven studies contributing to the quantitative meta-analysis were cross-sectional. Physical activity and epigenetic aging were therefore assessed without establishing which came first.
This makes it impossible to conclude from the meta-analysis that greater physical activity caused the lower epigenetic age acceleration.
More active people may differ from less active people in other ways that influence epigenetic aging.
The authors therefore called for longitudinal studies and clinical trials using standardised, objectively measured physical activity.
Such studies are needed to determine whether changing physical activity can actually modify aging trajectories and whether there is a measurable dose-response relationship.
Why It Matters for Longevity
Physical activity already has a strong evidence base for preventing disease and preserving health as people age.
The additional question is whether some of these benefits may also be reflected in molecular markers of aging.
This systematic review provides evidence that they may be.
Higher physical activity was associated with lower age acceleration on two established DNA methylation measures, including GrimAge.
That finding strengthens the biological connection between an active lifestyle and healthier aging.
At the same time, epigenetic clocks should not become the sole reason to exercise.
The established benefits of physical activity extend far beyond biological age measurements. Regular physical activity contributes to cardiovascular and metabolic health, physical capacity and the preservation of function across the lifespan.
Whether exercise can directly slow epigenetic aging remains an important scientific question.
The current evidence supports an association. Demonstrating causation will require longitudinal and interventional research.
Clinical Perspective
This study provides one of the most comprehensive assessments to date of physical activity and biological age measured by DNA methylation clocks.
The overall evidence points in a positive direction.
Across the systematic review, greater physical activity was generally associated with lower DNA methylation age. In the quantitative meta-analysis, statistically significant associations were found for both Horvath and GrimAge epigenetic age acceleration.
However, the magnitude of these associations was modest, and significant results were not observed for Hannum or PhenoAge.
This is clinically important because it demonstrates that “biological age” is not a single uniform measurement.
Different epigenetic clocks capture different biological signals. A favourable result on one clock does not necessarily mean that all dimensions of biological aging have changed.
The study also cannot determine how much physical activity would be required to influence epigenetic aging, whether particular types of exercise are more effective, or whether increasing physical activity causes a person’s epigenetic age to decline.
These questions require prospective studies and randomized clinical trials.
Key Takeaway
Higher physical activity was associated with a younger epigenetic aging profile, particularly on Horvath and GrimAge measures. The findings strengthen the evidence linking an active lifestyle with healthier aging, although a direct effect on biological aging has not yet been established.
Reviewed and Summarized by
Source Publication
- Title:
- Physical Activity and Biological Age: What Do DNA Methylation Clocks Show?
- Authors:
- Jiatong Shan, et al.
- Journal:
- The Lancet Healthy Longevity, April 2026.
