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 9 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 × LTPA interaction p = .041). In the high LTPA group, the trajectory declined significantly compared to the low (p = .004) and moderate LTPA groups (p = .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.