Combined effect of biological age and fine particulate matter pollution with risk of nonalcoholic fatty liver disease in the UK Biobank: a prospective cohort study

Aging and long-term exposure to fine particulate matter (PM2.5) are associated with a higher risk of nonalcoholic fatty liver disease (NAFLD), but evidence on their combined effect is limited. We thus evaluated the joint effects of accelerated biological aging and PM2.5 exposure on incident NAFLD in a UK cohort. We included 296 917 UK Biobank participants without NAFLD at baseline. Annual mean PM2.5 concentration was evaluated using a land use regression model. Biological age was assessed using the Klemera-Doubal method (KDM-BA) and PhenoAge algorithm. Cox proportional hazards models were used to assess the effects on incident NAFLD. Both chronic PM2.5 exposure and older biological age were linked to higher risk of NAFLD, with HRs of 1.07 (95% CI, 1.04-1.10) per SD increase in PM2.5, 1.47 (95% CI 1.43-1.52) in per SD increase KDM-BA, and 1.38 (95% CI 1.35-1.41) in per SD increase PhenoAge-BA, respectively. Participants with low PhenoAge and low PM2.5 had a lower NAFLD risk than those with high PhenoAge and high PM2.5. Positive additive interactions were observed. This study suggests that both PM2.5 exposure and biological aging increase NAFLD risk, with simultaneous exposure to high levels potentially intensifying their effects.