Journal
ENVIRONMENTAL EPIGENETICS
Volume 4, Issue 3, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eep/dvy017
Keywords
epigenetics; DNA methylation; aging; bisphenol A; high-fat diet; physical activity
Categories
Funding
- University of Michigan (UM) NIEHS/EPA Children's Environmental Health and Disease Prevention Center P01 [ES022844/RD83543601]
- Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) NIEHS Core Center [P30 ES017885]
- UM NIEHS [T32 ES007062, T32 HD079342, F31 ES025101]
- University of Michigan Nutrition Obesity Research Center [P30 DK089503]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [T32HD079342] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK020572, P30DK089503] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [T32ES007062, P30ES017885] Funding Source: NIH RePORTER
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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, LAP), two imprinted genes (Igf2, H19), and one non-imprinted gene (Esr1) in isogenic mice developmentally exposed to Control, Control + BPA (50 mu g/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). Esr1also 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.
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