Dietary pattern and epigenetic aging: a longitudinal twin study

Diet is an environmental factor influencing aging and life expectancy. Age-associated DNA methylation and epigenetic clocks are primary hallmarks of aging and may be modified by diet. However, observed associations between diet and epigenetic clocks may be confounded by familial factors. Using data from monozygotic twins in the Danish GEMINAKAR cohort, established in 1997-2000, when participants were aged 18-67 years, and with a 12-year follow-up, we examined whether adherence to Danish dietary guidelines is associated with epigenetic age independent of such confounding. Dietary intake was assessed at both time points using food frequency questionnaires, and adherence quantified by the Danish Dietary Index. Epigenetic age was estimated using established clocks (PCHannum, PCHorvath1, PCPhenoAge, and PCGrimAge) and DunedinPACE. We conducted both individual-level and within-twin-pair analyses using linear regression models to account for familial factors, assessing associations cross-sectionally and longitudinally. The analysis of monozygotic twins who share practically all their segregating genes and were subjected to the same early-life environment allowed us to account for genetic and shared environmental factors in the within-twin-pair analyses. Higher adherence to dietary guidelines was associated with lower epigenetic age(ing) in cross-sectional individual analyses, particularly for PCGrimAge (0.55-0.67 years lower PCGrimAge) and DunedinPACE (3.1% lower pace of aging) per 1 unit increase in index score. However, these associations were attenuated in within-twin-pair and longitudinal analyses, suggesting that they could be explained by genetic and shared environmental factors. Overall, the findings do not support strong independent associations but indicate that apparent benefits of dietary adherence on epigenetic aging may partly reflect familial factors.