Embracing a “Compound” Exposome Approach to Better Understand Environment and DNA Methylation Age Relationships

Abstract

BACKGROUND AND AIM: DNA methylation-based measures of aging remain a promising focus of research because they offer the possibility of detecting adverse changes in human physiology before the onset of clinical disease. This is particularly important in the context of environmental pollutants, because exposure to toxicants can often be intervened upon. METHODS: In a series of studies using data from male VA Normative Aging Study (NAS) and Mars-500 mission participants, we evaluated relationships of long-term environmental exposures with blood leukocyte measures of DNA methylation age. RESULTS:In NAS participants, an IQR increase in one-year PM2.5 (β = 0.64-years, 95%CI: 0.20, 1.09, P = 0.005), sulfate (β = 0.51-years, 95%CI: 0.28, 0.74, P 0.0001), and ammonium (β = 0.36-years, 95%CI: 0.02, 0.70, P = 0.04) were associated with increases in DNA methylation age. These relationships were significantly modified by endothelial function variant scores, mitochondrial haplogroups, and miRNA-processing alleles. In Mars-500 participants, mission duration was associated with decreases in DNA methylation aging (β = -5.41-years, 95%CI: −8.70, −2.12, P = 0.003). CONCLUSIONS:Still, it remains unclear if these relationships apply to all persons. Adopting an exposome approach that facilitates more comprehensive exposure-disease pathway characterizations across domains including the social exposome and neighborhood factors remains an important step to better understanding these and other DNA methylation age relationships with environmental factors. Exposome-centered study designs should also be supported with efforts to increase the recruitment and retention of racially diverse study populations and researchers, and further “compounded” with efforts to improve the use and interpretation of race throughout the publication and dissemination process. Such a “compound” exposome approach expands the ability of research to identify DNA methylation-based aging biomarkers that explicate racial disparities in health. A compound exposome approach also better positions the environmental research community to contribute to the elimination of racial health disparities. KEYWORDS: Epigenetic Aging, Exposome, Equity, DNA Methylation Age