2024

Kankaanpää, Anna

Ageing is a complex phenotype regulated by both genetic influences and environmental factors, such as modifiable lifestyle-related factors, over the life course. DNA methylation (DNAm)-based estimators, including ‘epigenetic clocks‘, are promising candidates for biomarkers of ageing. The purpose of this study was to investigate genetic and environmental influences on biological ageing using DNAm-based estimators at different ages. This thesis includes four studies based on data retrieved from the Finnish Twin Cohort (FTC). The FTC comprises three large cohort studies. The older FTC study included twins born before 1958, Finntwin16 focused on twins born from 1975–1979 and Finntwin12 examined twins born from 1983–1987. For the subsamples (N: ~2,600), DNAm levels were determined based on blood samples, and DNAm-based estimators were used to assess biological ageing in adulthood. Based on the results, biological ageing is highly heritable. Unhealthy lifestyles and overweight in adolescence were associated with accelerated biological ageing in young adulthood, but genetic factors largely explained the observed associations. Men were biologically older than women, and this sex difference increased with age. The difference was partially explained by more frequent smoking and a higher body mass index in men than in women. Leisure-time physical activity was associated with biological ageing, but this association seems to be susceptible to bias from multiple sources. The findings of this study suggest that DNAm-based estimators of biological ageing are valuable tools for epidemiological studies of life course, as they seem to capture the effects of lifestyle-related factors that accumulate over the life course. The confounding role of genetic factors and exposure to smoking should be carefully considered when using these measures.