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, the health effects of joint exposure to multiple metals are 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). We used mixed models and Bayesian kernel machine regression and controlled for participant sex, race, ethnicity, cigarette use, income, educational attainment, and block group poverty. We observed consistently positive estimates of the effects 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 an increase in serum lead or mercury from the 25th to 75th percentile is associated with a similar to 0.25-year increase in two epigenetic markers of all-cause mortality in a population of adults in Detroit, Michigan. While few of the findings were statistically significant, their consistency and novelty warrant interest.

Automated summary

The effects of lead, mercury, manganese, and copper on individual disease processes have been well understood. However, estimating the health effects of long-term exposure to these metals at low concentrations is difficult. This study aimed to estimate the effects of these metals on biomarkers of biological aging. The results showed positive associations between lead and GrimAge acceleration, and mercury and PhenoAge acceleration, while negative associations were found between manganese and PhenoAge acceleration, and mercury and Horvath Age acceleration. Additionally, curvilinear relationships were observed between copper and both PhenoAge and GrimAge acceleration. Increasing total exposure to the mixture of metals was associated with accelerated biological aging. Despite few statistically significant findings, the consistency and novelty of the results warrant further interest.