Combined Effect of Biological Age and Fine Particulate Matter Pollution with Risk of Non-Alcoholic Fatty Liver Disease in the UK Biobank: A Prospective Cohort Study

Abstract Background: Aging and long-term exposure to fine particulate matter (PM2.5) are associated with a higher risk of non-alcoholic 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. Methods: 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. Results: Both chronic PM2.5 exposure and older biological age were linked to higher risk of NAFLD, with hazard ratios (HR) 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. Conclusions: This study suggests that both PM2.5 exposure and biological aging increase NAFLD risk, with simultaneous exposure to high levels potentially intensifying their effects.