Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan
Although the effects of lead, mercury, manganese, and copper on individual disease processes are well understood, estimating the health effects of long-term exposure to these metals at the low concentrations often observed in the general population is difficult. In addition, although each of these metals may impact health individually, the health effects of joint exposure to multiple metals are more difficult to estimate. Biological aging refers to the integrative progression of multiple physiologic and molecular changes that make individuals more at risk of disease. Biomarkers of biological aging may be useful to estimate the population-level effects of metal exposure prior to the development of disease in the population. We used data from 290 participants in the Detroit Neighborhood Health Study to estimate the effect of serum lead, mercury, manganese, and copper on three DNA methylation-based biomarkers of biological aging (Horvath Age, PhenoAge, and GrimAge) using mixed models and Bayesian kernel machine regression and controlling for participant gender, race, ethnicity, cigarette use, income, educational attainment, and block group poverty. We found consistently positive estimates of effect between lead and GrimAge acceleration and mercury and PhenoAge acceleration. In contrast, we observed consistently negative associations between manganese and PhenoAge acceleration and mercury and Horvath Age acceleration. We also observed curvilinear relationships between copper and both PhenoAge and GrimAge acceleration. Increasing total exposure to the observed mixture of metals was associated with increased PhenoAge and GrimAge acceleration and decreased Horvath Age acceleration. These findings indicate that lead and mercury are associated with an approximate 0.25-year increase in two epigenetic markers of all-cause mortality in a population of adults in Detroit, Michigan.