Environmental exposures and biological ageing

Objective: Environmental factors may influence health by altering cellular function. Epigenetic clocks, DNA methylation–based biomarkers of biological ageing, offer a potential mechanistic link between environmental exposures and health outcomes. Although associations with specific exposures have been reported, comprehensive assessments across diverse and highly correlated environmental domains remain limited. This study examined the relationships between wide range of environmental exposures and biological ageing

Methods: Data came from Understanding Society, a nationally representative UK panel survey. Five epigenetic clocks (Horvath, Hannum, PhenoAge, DunedinPoAm, DunedinPACE) were derived from blood samples collected during nurse visits in 2010 and 2012. Over 30 high resolution indicators covering social, built, retail, health, and physico chemical, and weather-related environments were linked to participants’ residential addresses. We constructed principal components for exposure domains, identified environmental clusters using k means, fitted single exposure and domain specific models, and performed variable selection using elastic net regression.

Results: The analytic sample included 3307 individuals (mean age 49y; 54% female). After adjustment for confounders and multiple testing, deprivation, crime, social cohesion, population density, greenness, distance to leisure and gambling facilities, PM2.5, PM10, NO2, O3 and temperature were significantly associated with second- and third-generation clocks, with relatively strong and consistent associations for DunedinPACE. Elastic net confirmed the selection of many environmental variables. Social environment (b=0.100), built environment (b=0.007), and air pollution domains (b=0.013) were associated with faster pace of ageing (DunedinPACE) even after adjusting for health behaviour; air pollution remained significant after adjusting for all other domains (b=0.014). Two exposure clusters were identified, with the rural cluster associated with slower ageing (DunedinPoAm: b=-0.008; DunedinPACE: b=-0.011).

Conclusions: This large, comprehensive study demonstrates that the external exposome, particularly social and built environments and air pollution, is associated with accelerated biological ageing. Longitudinal studies are needed to investigate mediation pathways, exposure trajectories, and environmental inequalities.