Associations of single and combined exposure to plasma metals with biological aging in Chinese adults: Mediation by inflammation and oxidative stress and moderation by diabetes.

This cross-sectional study examined the single and combined associations of plasma metals with biological aging and explored the potential mediating roles of inflammation and oxidative stress, as well as the modifying effect of diabetes. Seventeen plasma metals and four biological age acceleration metrics (KDM_accel, PhenoAge_accel, PAI_accel, and homeostatic dysregulation (HD)) were assessed in 3055 Chinese volunteers. Generalized linear model, generalized additive model, least absolute shrinkage and selection operator, weighted quantile sum (WQS), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were employed to evaluate individual and combined effects. Plasma Cu and Sr showed positive associations with at least two aging indicators, whereas V, Fe, and Zn were negatively associated with aging. The metal mixture consistently exhibited linear and positive associations with KDM_accel and HD (predominantly driven by Cu, Se, and Sb), as revealed by WQS, qgcomp, and BKMR. Meanwhile, the metal mixture showed complex nonlinear relationships with PhenoAge_accel and PAI_accel. Cu and Co were the primary positive contributors to PhenoAge and PAI, whereas V and Fe were the primary negative contributors. Inflammation and oxidative stress were found to partially mediate the associations between metals and aging. Additionally, diabetes, a metabolic disease accompanied by inflammation and oxidative stress, was related to accelerated aging and significantly modified the metal-aging relationships. These findings suggest that exposure to metals is associated with biological aging, with dose-response patterns depending on the specific metal and aging indicator. Future prospective research is necessary to confirm these associations and further elucidate the roles of inflammation, oxidative stress, and diabetes in metal-aging associations.