Purpose: Greater leisure-time physical activity (LTPA) associates with healthier lives, but knowledge regarding occupational physical activity (OPA) is more inconsistent. DNA methylation (DNAm) patterns capture age-related changes in different tissues. We aimed to assess how LTPA and OPA are associated with three DNAm based epigenetic age estimates, namely DNAm Age, PhenoAge and GrimAge.

Methods: The participants were young adult (21-25-year-old, n = 285) and older (55-74-year-old, n = 235) twin pairs, including 16 pairs with documented long-term LTPA discordance. Genome-wide DNAm from blood samples was used to compute DNAm Age, PhenoAge and GrimAge Age acceleration (Acc), which describes the difference between chronological and epigenetic ages. Physical activity was assessed with sport, leisure-time and work indices based on the Baecke Questionnaire. Genetic and environmental variance components of epigenetic age Acc were estimated by quantitative genetic modelling.Epigenetic age Acc was highly heritable in young adult and older twin pairs (~60%). Sport index was associated with slower and OPA with faster DNAm GrimAge Acc after adjusting the model for sex. Genetic factors and non-shared environmental factors in common with sport index explained 1.5-2.7% and 1.9-3.5%, respectively, of the variation in GrimAge Acc. The corresponding proportions considering OPA were 0.4-1.8% and 0.7-1.8%, respectively. However, these proportions were minor (<0.5%) after adjusting the model for smoking status.

Conclusions: LTPA associates with slower and OPA with faster epigenetic aging. However, adjusting the models for smoking status, which may reflect the accumulation of unhealthy lifestyle habits, attenuated the associations.