Association of the essential metal mixture with biological aging in Chinese older adults: Investigating superoxide dismutase as a potential mediator

The joint association of essential metals (EMs) with biological aging and the potential mediating role of antioxidant biological processes remain poorly understood. We aimed to investigate the association of a multi-matrix EM mixture with biological aging and to assess the potential statistical mediation by superoxide dismutase (SOD). This cross-sectional study recruited 2787 Chinese older adults. Blood concentrations of five EMs (manganese-Mn, copper-Cu, zinc-Zn, selenium-Se, rubidium-Rb) and urinary concentrations of four EMs (molybdenum-Mo, calcium-Ca, magnesium-Mg, strontium-Sr) were measured. Biological aging was assessed using KDM-biological age acceleration (KDM-accel), a clinical biomarker-based measure of systemic physiological decline. Associations were evaluated using linear regression, generalized additive models (GAMs), weighted quantile sum (WQS), quantile-based g-computation (QGC), and Bayesian kernel machine regression (BKMR) models. Bioinformatic and statistical mediation analyses were used to explore potential biological process and the role of SOD. In mixture analysis, a quartile increase in the EM mixture was significantly associated with a 1.77-year (95% CI = -2.43, -1.12) decrease in KDM-accel. Mg, Rb, and Mn were the primary contributors to this negative association, whereas Cu was associated with accelerated aging. Bioinformatic analysis revealed a link between these key EMs and oxidative stress. Statistical mediation analysis indicated a significant mediating role for SOD, with proportions of 4.9% for the mixture, 7.2% for Rb, and 15.0% for Mn. A biological profile characterized by higher levels of Mg, Rb, and Mn and lower Cu is associated with decelerated biological aging in older adults, and this relationship is partly statistically explained by the antioxidant activity of SOD. Our findings highlight the importance of considering EM mixture and their underlying redox process in aging research.