Leisure-time physical activity and metabolomic trajectories over the transition from late midlife to old age

Physical activity may counteract aging-associated disruptions in the metabolome. We investigated how leisure-time physical activity (LTPA) associates with the metabolome in late midlife and with 15-year metabolomic trajectories. The study included 1816 Helsinki Birth Cohort Study participants at baseline (mean age 61.6 years), with 985, 996, and 740 participants at the 5-, 10-, and 15-year follow-ups, respectively. LTPA was assessed at baseline and after 15 years using a validated questionnaire and expressed as METhours/week. Nuclear magnetic resonance-based metabolomics data from fasting blood samples were used to analyze 161 biomarkers at baseline and at each follow-up. Weighted Gene Co-Expression Network Analysis was performed on the metabolomics data to identify 11 metabolomic biomarker modules. Baseline associations were analyzed using restricted cubic splines and longitudinal associations with linear mixed-effects models. Analyses were sex-stratified, covariate-adjusted, and corrected for multiple testing. At baseline, LTPA was nonlinearly associated with albumin in women and with nine biomarkers in men in the crude, but not fully adjusted, model. Over the follow-up, baseline LTPA was associated with the age-related trajectory of triglyceride-enriched high-density lipoprotein (HDL) module in men (age x LTPA interaction p = 0.041). In the high LTPA group, the trajectory declined significantly compared to the low (p = 0.004) and moderate LTPA groups (p = 0.045). No associations were found in women. To conclude, in men, higher LTPA in late midlife predicted a favorable 15-year trajectory of triglyceride-enriched HDL. Our findings indicate that an active lifestyle is associated with more favorable metabolomic trajectories related to cardiometabolic health across late midlife and old age.