Physical activity is associated with slower epigenetic ageing—Findings from the Rhineland study

Abstract

Epigenetic ageing, i.e., age‐associated changes in DNA methylation patterns, is a sensitive marker of biological ageing, a major determinant of morbidity and functional decline. We examined the association of physical activity with epigenetic ageing and the role of immune function and cardiovascular risk factors in mediating this relation. Moreover, we aimed to identify novel molecular processes underlying the association between physical activity and epigenetic ageing. We analysed cross‐sectional data from 3567 eligible participants (mean age: 55.5 years, range: 30–94 years, 54.8% women) of the Rhineland Study, a community‐based cohort study in Bonn, Germany. Physical activity components (metabolic equivalent (MET)‐Hours, step counts, sedentary, light‐intensity and moderate‐to‐vigorous intensity activities) were recorded with accelerometers. DNA methylation was measured with the Illumina HumanMethylationEPIC BeadChip. Epigenetic age acceleration (Hannum's age, Horvath's age, PhenoAge and GrimAge) was calculated based on published algorithms. The relation between physical activity and epigenetic ageing was examined with multivariable regression, while structural equation modeling was used for mediation analysis. Moreover, we conducted an epigenome‐wide association study of physical activity across 850,000 CpG sites. After adjustment for age, sex, season, education, smoking, cell proportions and batch effects, physical activity (step counts, MET‐Hours and %time spend in moderate‐to‐vigorous activities) was non‐linearly associated with slower epigenetic ageing, in part through its beneficial effects on immune function and cardiovascular health. Additionally, we identified 12 and 7 CpGs associated with MET‐Hours and %time spent in moderate‐to‐vigorous activities, respectively (p < 1 × 10−5). Our findings suggest that regular physical activity slows epigenetic ageing by counteracting immunosenescence and lowering cardiovascular risk.

Organ specificity and commonality of epigenetic aging in low- and high-running capacity rats

“…Previous research has demonstrated the influence of acute and regular exercise on global and gene-specific promoter methylation, primarily in peripheral blood and skeletal muscle 5,6 . Recent findings, including those of our study, also indicate a negative relationship between physical fitness (including activity levels and CRF) and epigenetic aging based on age-related changes in DNA methylation levels at CpG sites 7–10 . These lines of evidence suggest that exercise exerts a rejuvenating effect on epigenetic aging and has a favorable effect on the aging process.…”

“…Cross-sectional studies in human populations have shown that physical activity and CRF are associated with delayed epigenetic age progression [7][8][9][10] . In mice, late-life exercise training may delay skeletal muscle epigenetic aging via skeletal muscle-specific epigenetic clock(s) 35,36 .…”

Associations between cardiorespiratory fitness and lifestyle‐related factors with DNA methylation‐based ageing clocks in older men: WASEDA'S Health Study

“…et al, 2011). In fact, a recent report indicates that the health benefits on biological ageing of additional physical activity are likely to be greatest in adults who lead sedentary lifestyles (Fox et al, 2023).…”

“…Therefore, the relationships between physical activity and respective DNAmAgeAccel have been investigated. Specifically, some previous studies have reported a marginal negative relationship between physical activity and DNAmAgeAccel after adjusting for confounding factors (Fox et al, 2023;Kankaanpää et al, 2021; smoking, alcohol consumption, disease status, sleep status, and chronotype. Both oxygen uptake at ventilatory threshold (VO 2 /kg at VT) and peak oxygen uptake (VO 2 /kg at Peak) showed a significant negative correlation with GrimAgeAccel, even after adjustments for chronological age and smoking and drinking status.…”

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

“…In addition, determining biological age can be helpful for identifying the individual health status and risk for age-related diseases (Fox et al, 2023). Furthermore, the use of methylation clocks has provided fundamental insights into some long-lived species that were previously thought to be "non-aging," such as the naked mole rat (Heterocephalus glaber).…”