Associations of non-essential metal mixture with biological aging and the mediating role of inflammation in Chinese older adults

BACKGROUND: Individual non-essential metals (NMs) have been linked with biological aging. However, the effects of NM mixture and their mechanisms remain unclear. OBJECTIVE: To characterize the relationships of individual NMs and their mixture to biological aging, and to explore the mediating roles of inflammatory factors. METHODS: This cross-sectional study recruited 3251 individuals aged 60 years or above in China. Urine gallium, arsenic, cadmium, cesium, thallium, and barium were tested using ICP-MS. The Klemera-Doubal method was used to construct the KDMAge, reflecting the estimation of biological age, and ΔKDMAge, defined as the difference between KDMAge and chronological age, reflecting the deviation in aging rate. Four blood cell counts, including neutrophil, lymphocyte, platelet, and monocyte, were used to calculate inflammatory indices: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and systemic immune-inflammation index. Linear regression, generalized additive model (GAM), weighted quantile sum (WQS), quantile-based computation (QGC), and Bayesian kernel machine regression (BKMR) were employed to assess the associations between the NMs and ΔKDMAge. Mediation analysis was further performed to examine the roles of inflammatory factors. RESULTS: KDMAge strongly correlated with chronological age (r = 0.863). Linear regression showed significant positive associations of Gallium (β = 0.88, 95 % CI = 0.30, 1.46), arsenic (β = 1.11, 95 % CI = 0.54, 1.69), and cesium (β = 0.75, 95 % CI = 0.19, 1.30) with ΔKDMAge. GAMs further exhibited a "J-shaped" relationship for gallium, arsenic with ΔKDMAge, a linear trend for cesium, and a "U-shaped" relationship for barium. The mixture models demonstrated a positive association between the NM mixture and ΔKDMAge, with gallium, arsenic, and cesium identified as the primary contributors. Mediation analyses further suggested that neutrophil-to-lymphocyte ratio and systemic immune-inflammation index partially mediated this association. CONCLUSIONS: The NM mixture accelerates biological aging, mainly driven by gallium, arsenic, and cesium, with partial mediation by inflammation. Future longitudinal studies are necessary to verify these findings.