Long-term ambient benzene exposure increases incident NAFLD risk through accelerated biological aging

The contribution of ambient air pollutants to non-alcoholic fatty liver disease (NAFLD) remains undefined. This study included 401,472 adults from the UK Biobank (UKB), with residential benzene estimated at 1-km resolution from the DEFRA model (2006-2020). After multivariable adjustment in the Cox models, each interquartile-range (0.151 μg/m3) increment in benzene was associated with a 26% higher risk of incident NAFLD (hazard ratio [HR] = 1.26; 95% confidence interval [CI], 1.21-1.30), following a nonlinear exposure-response relationship. Accelerated biological aging mediated 6.5% of this association, whereas homeostatic dysregulation and allostatic load contributed modestly. Benzene exposure and polygenic risk showed no multiplicative interaction, but their cumulative effect raised NAFLD risk among highly susceptible individuals. A machine-learning model integrating benzene and covariates predicted NAFLD with good discrimination (AUC = 0.753), and an external urinary-biomarker analysis in NHANES was directionally consistent. Thus, long-term low-level benzene exposure increases incident NAFLD risk, partly through accelerated biological aging.