Biological aging mediates the associations of metals exposure and cognitive function: Results from a large...

Biological aging may be a key pathway linking environmental exposures to cognitive decline, but it remains poorly understood. The study aimed to explore the effects of multiple metals co-exposure on biological aging and the mediating effects of biological aging on the metal-cognition associations. Among 5979 Chinese adults aged ≥ 50 years, we estimated biological aging by using two validated indices: KDM-accel (based on the Klemera and Doubal method) and physiological dysregulation (PD, derived via Mahalanobis distance). We measured their plasma concentrations of 23 metals and assessed their cognitive function by using Mini-Mental State Examination (MMSE). The results showed that accelerated biological aging was significantly associated with lower MMSE score [KDM-accel: β (95% CI) = -0.194 (-0.279, -0.109); PD: -0.180 (-0.258, -0.102)]. The plasma levels of iron (Fe) and zinc (Zn) showed inverse associations with both KDM-accel and PD, while strontium (Sr) showed a positive association with both indices (all FDR < 0.05). Compared to high Zn group, a stronger positive association between Sr and KDM-accel was observed in the low Zn group [β (95% CI) = 0.494 (0.128, 0.860) vs. 1.453 (1.083, 1.823), P-int < 0.001]. Mediation analysis indicated that KDM-accel and PD may account for 5.51% and 15.65% of the Fe-cognition association, as well as 7.16% and 12.92% of the Zn-cognition association, which suggested potential indirect pathways. This study identified the effects of Fe, Sr, Zn, and their co-exposure on biological aging, and suggested that biological aging deceleration may partially explain the associations of Fe and Zn with better cognition.