Longitudinal effects of developmental bisphenol A, variable diet, and physical activity on age-related methylation in blood. Issue 3 (19th July 2018)

• Record Type: Journal Article
• Authors: Kochmanski, Joseph; Marchlewicz, Elizabeth H; Dolinoy, Dana C
• Editors: Nagel, Susan
• Is Part Of: Environmental epigenetics. Volume 4:Issue 3(2018)
• Publication Date: 2018-07-19
• Subjects: epigenetics -- DNA methylation -- aging -- bisphenol A -- high-fat diet -- physical activity; Epigenetics -- Periodicals; 572.86505
• DOI: 10.1093/eep/dvy017
• Languages: English
• ISSNs: 2058-5888

Abstract

Abstract: Research indicates that environmental factors can alter DNA methylation, but the specific effects of environmental exposures on epigenetic aging remain unclear. Here, using a mouse model of human-relevant exposures, we tested the hypothesis that early-life exposure to bisphenol A (BPA), variable diet, and/or changes in physical activity would modify rates of age-related methylation at several target regions, as measured from longitudinal blood samples (2, 4, and 10 months old). DNA methylation was quantified at two repetitive elements (LINE-1, IAP), two imprinted genes ( Igf2, H19 ), and one non-imprinted gene ( Esr1 ) in isogenic mice developmentally exposed to Control, Control + BPA (50 µg/kg diet), Western high-fat diet (WHFD), or Western + BPA diets. In blood samples, Esr1 DNA methylation increased significantly with age, but no other investigated loci showed significant age-related methylation. LINE-1 and IAP both showed significant negative environmental deflection by WHFD exposure ( P < 0.05). Esr1 also showed significant negative environmental deflection by WHFD exposure in female mice ( P = 0.02), but not male mice. Physical activity had a non-significant positive effect on age-related Esr1 methylation in female blood, suggesting that it may partially abrogate the effects of WHFD on the aging epigenome. These results suggest that developmental nutritional exposures can modify age-related DNA methylation patterns at a gene related to growth and development. As such, environmental deflection of the aging epigenome may help to explain the growing prevalence of chronic diseases in human populations.