DNA methylation signatures in peripheral blood mononuclear cells from a lifestyle intervention for women at midlife: A pilot RCT

Objectives: Physical activity confers many health benefits, but the underlying mechanisms require further exploration. In this pilot randomized controlled trial we tested the association between longitudinal measures of DNA methylation and changes in objective measures including physical activity, weight loss, and C-reactive protein levels in community-dwelling women aged 55 to 70 years. Methods: We assessed DNA methylation from 20 healthy post-menopausal women (55-70 years of age), who did not have a mobility disability and allocated them to a group-based intervention, Everyday Activity Supports You (EASY), or a control group (monthly group-based health-related education sessions). The original randomized controlled trial was six months in duration and consisted of nine sessions of two-hour focused on reducing sedentary behavior for the intervention group, or six one-hour sessions on other topics for the control group. We collected peripheral blood mononuclear cells, both at baseline and six months later. Samples were processed using the Illumina 450k Methylation array to quantify DNA methylation at >485,000 CpG sites in the genome. Results: There were no significant associations between DNA methylation and physical activity, but we did observe alterations at epigenetic modifications that correlated with change in percent body weight over a six-month period at 12 genomic loci, two of which are located near the previously reported weight-associated genes RUNX3 and NAMPT. We also generated a potential epigenetic predictor of weight loss using baseline DNA methylation at five CpG sites. Conclusions: These exploratory findings suggest a potential biological link between body weight changes and epigenetic processes.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author