Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan

Evans K Lodge; Radhika Dhingra; Chantel L Martin; Rebecca C Fry; Alexandra J White; Cavin K Ward-Caviness; Agaz H Wani; Monica Uddin; Derek E Wildman; Sandro Galea; Allison E Aiello

doi:10.1093/eep/dvac018

Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan

Environ Epigenet. 2022 Sep 21;8(1):dvac018. doi: 10.1093/eep/dvac018. eCollection 2022.

Authors

Evans K Lodge^{1

2

3}, Radhika Dhingra^{4

5}, Chantel L Martin^{1

2

6}, Rebecca C Fry^{4

6}, Alexandra J White⁷, Cavin K Ward-Caviness⁸, Agaz H Wani⁹, Monica Uddin⁹, Derek E Wildman⁹, Sandro Galea¹⁰, Allison E Aiello^{1

2}

Affiliations

¹ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC 27599, USA.
² Carolina Population Center, University of North Carolina at Chapel Hill, 123 W Franklin St, Chapel Hill, NC 27516, USA.
³ School of Medicine, University of North Carolina at Chapel Hill, 321 S Columbia St, Chapel Hill, NC 27599, USA.
⁴ Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC 27599, USA.
⁵ Institute for Environmental Health Solutions, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC 27599, USA.
⁶ Center for Environmental Health & Susceptibility, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC 27599, USA.
⁷ Epidemiology Branch, National Institute of Environmental Health Sciences, A323 David P Rall Building, Research Triangle Park, NC 27709, USA.
⁸ Center for Public Health and Environmental Assessment, US Environmental Protection Agency, 104 Mason Farm Rd, Chapel Hill, NC 27514, USA.
⁹ Genomics Program, College of Public Health, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA.
¹⁰ School of Public Health, Boston University, 715 Albany St, Boston, MA 02118, USA.

Abstract

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 ∼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.

Keywords: DNA methylation; copper; epigenetic age; lead; manganese; mercury.

Abstract

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