Socioenvironmental Causes of Elevated Toxic Metal Levels and Epigenetic Aging

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Project Summary: Reducing human exposure to toxic metals is a national and global public health priority. The risk of exposure to toxic metals is unevenly distributed across the United States, with a much higher burden of exposure to many industrial pollutants in densely populated urban areas among individuals of lower socioeconomic position and minority race. Although links between individual characteristics (socioeconomic position, occupation, access to clean water, etc.) and biomarkers of elevated toxic metals have been previously established, few studies have investigated the effect of large-scale social, economic, and environmental changes on serum metal levels. Given rapid changes in many American urban areas due to industrial activity and deindustrialization, understanding the population-level risks posed by urban industrial environmental pollution and neighborhood socioenvironmental change is imperative to mitigate the effects of toxic metals on population health. The objectives of this proposal are to (1) characterize the effects of urban socioenvironmental changes on individual and joint serum lead (Pb), mercury (Hg), chromium (Cr), and manganese (Mn), and (2) assess the individual and simultaneous effects of Pb, Hg, Cr, and Mn on epigenetic aging. Longitudinal data from 779 participants in the 2008-2013 Detroit Neighborhood Health Study (DNHS) and data on location-specific urban environmental pollutants from the American Community Survey, Michigan Department of Environmental Quality, and Michigan Department of Transportation will be used to assess the effects of block group building quality, vacant housing, brownfield pollution, and commercial traffic density on longitudinal measures of serum Pb, Hg, Cr, and Mn. Longitudinal measures of epigenetic age generated from DNA methylation analysis will be used to assess the individual and joint effects of Pb, Hg, Cr, and Mn on accelerated biological aging. The completion of the proposed aims will significantly advance our understanding of the burden of metal exposures in urban America, as well as their individual and joint effects on epigenetic aging, an accurate predictor of all-cause mortality. The DNHS provides an excellent opportunity to conduct the proposed research using longitudinal data from a representative sample of adults in a heavily industrialized city undergoing significant redevelopment. The training plan outlined in this F30 proposal will equip the applicant with the necessary skills in social, environmental, and epigenetic epidemiology and clinical medicine to successfully complete the proposed aims and progress into a role as a physician-scientist studying the interrelated effects of social disadvantage and environmental pollution on population health in the United States. The applicant is extremely well supported by an interdisciplinary group of epidemiologists, toxicologists, environmental scientists, geographers, and clinicians with the requisite expertise to support his clinical training and doctoral research.