Multidomain residential external exposome and epigenetic ageing in the UK general population

Residential environmental exposures might be associated with biological ageing, but evidence has largely focused on a limited set of single exposures. We investigated associations between the multidomain residential external exposome and epigenetic ageing in 3307 adults from the nationally representative UK Understanding Society study. We linked 30 exposures across six domains spanning social, built, physico-chemical, retail, health and weather environments, to residential postcodes and examined associations with first-, second- and third-generation epigenetic clocks. Across four complementary approaches capturing individual, joint, domain-level and clustered exposures, adverse social, built and physico-chemical environments showed the most consistent associations with biological ageing. Area deprivation, neighbourhood crime, lower social cohesion and greenness, air pollution and higher temperatures were associated with faster pace of ageing measured by third-generation clocks (particularly DunedinPACE) and, to a lesser extent, with PhenoAge. Greater distance to leisure services was associated with older biological age on Horvath s clock and PhenoAge. Clustering identified urban and rural exposure profiles, with faster ageing in the urban profile. Residential environmental exposures are associated with epigenetic ageing, with later-generation clocks appearing more sensitive to the biological imprint of the external residential exposome.