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

Abstract

DNA methylation‐based age estimators (DNAm ageing clocks) are currently one of the most promising biomarkers for predicting biological age. However, the relationships between cardiorespiratory fitness (CRF), measured directly by expiratory gas analysis, and DNAm ageing clocks are largely unknown. We investigated the relationships between CRF and the age‐adjusted value from the residuals of the regression of DNAm ageing clock to chronological age (DNAmAgeAcceleration: DNAmAgeAccel) and attempted to determine the relative contribution of CRF to DNAmAgeAccel in the presence of other lifestyle factors. DNA samples from 144 Japanese men aged 65–72 years were used to appraise first‐ (i.e., DNAmHorvath and DNAmHannum) and second‐ (i.e., DNAmPhenoAge, DNAmGrimAge, and DNAmFitAge) generation DNAm ageing clocks. Various surveys and measurements were conducted, including physical fitness, body composition, blood biochemical parameters, nutrient intake, smoking, alcohol consumption, disease status, sleep status, and chronotype. Both oxygen uptake at ventilatory threshold (VO2/kg at VT) and peak oxygen uptake (VO2/kg at Peak) showed a significant negative correlation with GrimAgeAccel, even after adjustments for chronological age and smoking and drinking status. Notably, VO2/kg at VT and VO2/kg at Peak above the reference value were also associated with delayed GrimAgeAccel. Multiple regression analysis showed that calf circumference, serum triglyceride, carbohydrate intake, and smoking status, rather than CRF, contributed more to GrimAgeAccel and FitAgeAccel. In conclusion, although the contribution of CRF to GrimAgeAccel and FitAgeAccel is relatively low compared to lifestyle‐related factors such as smoking, the results suggest that the maintenance of CRF is associated with delayed biological ageing in older men.

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

“…Our previous study also found a significant negative relationship between CRF and age acceleration, but this study included only men 9 . Most other previous studies have examined the relationship between physical activity and age acceleration in the same cohort of men and women (adjusted for sex) through cross-sectional designs 9 . Considering the overall findings of previous studies that suggest that exercise may delay epigenetic age progression, the relationship between exercise and multi-organ epigenetic age is worth investigating, along with the development of a rat clock that can capture biological aging with high precision across multiple organs, as well as their sex differences.…”

“…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 .…”

Healthy aging: Linking causal mechanisms with holistic outcomes

“…The link between CRF and DNA methylation clocks is also an emerging area of research, bridging physical fitness with molecular biomarkers that measure the rate or pace of aging. Kawamura et al (2023) describe associations between CRF and lifestyle-related factors with DNA methylation in a cohort of older men, finding that higher CRF levels correlated with delayed biological aging, though lifestyle factors (e.g., smoking) had a more significant impact, highlighting the nuanced interplay between fitness, behavioral exposures, and biological aging.…”

Healthy Japanese Dietary Pattern Is Associated with Slower Biological Aging in Older Men: WASEDA’S Health Study

“…The procedure from blood collection to sample storage has been described previously (15, 31). The participants were instructed to fast for at least 12 h the night before blood collection.…”

“…Accumulating evidence suggests that the epigenetic clock is associated with lifestyle factors, such as body composition (11), physical activity (12,13) and physical fitness levels (14,15), smoking (16), and alcohol intake (16), and can be delayed or reversed by pharmacological and lifestyle interventions (17)(18)(19)(20). It has also been suggested that healthy dietary patterns, diets rich in fruits and vegetables, and mediterranean diets may delay the epigenetic clocks (21)(22)(23)(24)(25)(26).…”