Life-course exposure to air pollution and biological ageing in the Lothian Birth Cohort 1936

Background: Exposure to ambient air pollution is associated with a range of diseases. Biomarkers derived from DNA methylation (DNAm) indicate a potential pathway to human health differences, connecting disease pathogenesis and biological ageing. However, little is known about sensitive periods during the life course where air pollution might have a stronger impact on DNAm, or whether effects accumulate over time. Objectives: We examined associations between air pollution exposure across the life course and DNAm-based biomarkers of ageing. Methods: Data were derived from the Lothian Birth Cohort 1936. Participants residential history was linked to annual levels of PM2.5, SO2, NO2, and O3 around 1935, 1950, 1970, 1980, 1990, and 2001; pollutant concentrations were estimated using the EMEP4UK atmospheric chemistry transport model. Blood samples were obtained between ages of 70 and 80 years, and Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, DNAmGrimAge, and DNAm telomere length (DNAmTL) were computed. We applied the structured life-course modelling approach: least angle regression identified best-fit life-course models for a composite measure of air pollution (air quality index [AQI]), and mixed-effects regression estimated selected models for AQI and single pollutants. Results: We included 525 individuals with 1782 observations. In the total sample, increased air pollution around 1970 was associated with higher epigenetic age (AQI: b=0.622 year, 95%CI: 0.151, 1.094) measured with Horvath DNAmAge in late adulthood. We found shorter DNAmTL among males with higher air pollution around 1980 (AQI: b=-0.035 kilobase, 95%CI: -0.057, -0.014) and among females with higher exposure around 1935 (AQI: b=-0.036 kilobase, 95%CI: -0.059, -0.013). Findings passed false discovery rate correction for DNAmTL, and were more consistent for the pollutants PM2.5, SO2 and NO2. Discussion: We tested the life-course relationship between air pollution and DNAm-based biomarkers. Air pollution in utero and in young-to-mid adulthood is linked to accelerated epigenetic ageing and telomere-associated ageing in later life.