Biological aging as a mediator of the association between air pollution and all-cause mortality and hospitalization: Evidence from the UK Biobank and Lifelines cohorts

Air pollution is a major environmental risk factor for premature mortality and hospitalization, yet the biological pathways linking pollution exposure to disease and mortality remain incompletely understood. We investigated whether biological aging mediates the effects of long-term air pollution exposure on mortality and hospitalizations using data from the UK Biobank (n = 309,467; aged 37-73 years) and the Lifelines (n = 29,146; aged 18-93 years). Long-term residential exposures to PM₂.₅, PM₁₀, and NO₂ were estimated using land-use regression and dispersion models. Biological aging was quantified using the Klemera-Doubal Method, PhenoAge, and frailty index. Mediation analyses were conducted for hospitalization in both cohorts and all-cause mortality in the UK Biobank, adjusting for demographic and socioeconomic factors. Higher air pollution exposure was associated with accelerated biological aging. Biological aging mediated 11.5-52.3% of the association between air pollution and mortality and 7.5-25.4% of the association with hospitalization in the UK Biobank. In Lifelines, PM₂.₅ was positively associated with frailty, with evidence of mediation for PM₁₀. These findings suggest that long-term exposure to air pollution may accelerate biological aging even at relatively low levels typical of European countries and contribute to pollution-related morbidity and mortality.