Cumulative Environmental Exposures and Accelerated Biological Aging

Abstract

Background: New methods for understanding biological pathways by which social and physical environments intersect to exacerbate disease processes and contribute to health disparities are needed. Epigenetic clocks derived from DNA methylation patterns are a novel tool to measure biological aging in comparison to chronological age. We used two different epigenetic clocks (Horvath and Levine) to determine the impact of chemical and social exposures on accelerated biological aging. Methods:Data from 620 Survey of the Health of Wisconsin participants were analyzed to examine associations between self-reported neighborhood-related stress, ambient air pollution, lead exposure, and smoking status and accelerated biological aging. The “Horvath clock” includes 351 CpGs that are highly correlated with chronological age and is the most commonly-used biological aging measure. The DNA Phenotypic Age or “Levine clock” includes 513 CpGs correlated with several blood biomarkers predictive of premature mortality. Only 41 CpG sites are included in both clocks. DNA methylation was measured using the Illumina 850K EPIC chip array. Accelerated aging was calculated via the residuals produced by regressing each biological age metric on chronological age. Results:After adjustment for gender, BMI, education and income, self-reported stress from living in a neighborhood (β=.54, p<.04) and smoking (β=1.59, p<.000) were both associated with accelerated biological aging using the Levine clock. Only smoking (β=.50, p<.04) was associated with the Horvath clock. Adjustments for physical activity reduced associations with neighborhood stress. Conclusions:Epigenetic clocks may capture accelerated biological aging associated with social stress and smoking but not environmental exposures at or below background population levels. Findings suggest that the Levine clock may be more sensitive to measuring the impact of social factors on aging. Epigenome-wide associations studies are needed to identify specific functional pathways and CpG sites that better epigenetic indicators more reflective of both chemical and social impacts on health and aging.