Objectives: The association between leisure-time physical activity (LTPA) and a lower risk of mortality is susceptible to bias from multiple sources. We investigated the potential of biological ageing to mediate the association between long-term LTPA and mortality and whether the methods used to account for reverse causality affect the interpretation of this association.
Methods: Study participants were twins from the older Finnish Twin Cohort (n=22,750; 18-50 years at baseline). LTPA was assessed using questionnaires in 1975, 1981 and 1990. The mortality follow-up lasted until 2020 and biological ageing was assessed using epigenetic clocks in a subsample (n=1,153) with blood samples taken during the follow-up. Using latent profile analysis, we identified classes with distinct longitudinal LTPA patterns and studied differences in biological ageing between these classes. We employed survival models to examine differences in total, short-term and long-term all-cause mortality, and multilevel models for twin data to control for familial factors.
Results: We identified four classes of long-term LTPA: sedentary, moderately active, active and highly active. Although biological ageing was accelerated in sedentary and highly active classes, after adjusting for other lifestyle-related factors, the associations mainly attenuated. Physically active classes had a maximum 7% lower risk of total mortality over the sedentary class, but this association was consistent only in the short term and could largely be accounted for by familial factors. LTPA exhibited less favourable associations when prevalent diseases were exclusion criteria rather than covariate.
Conclusion: Being active may reflect a healthy phenotype instead of causally reducing mortality.