EXERCISE TRAINING-INDUCED CHANGES ON DNA METHYLATION IN MILD COGNITIVELY IMPAIRED OLDER AFRICAN AMERICANS: GEMS STUDY

Abstract

DNA methylation at CpG sites is an important epigenetic modification of the human genome that can affect gene expression and potentially influence health outcomes. Notably, aging and physical exercise have been shown to influence epigenetic modification with during minimal exercise, inducing hypomethylation of the entire genome within muscle cells. However, there is paucity of data on exercise-induced training adaptation on DNA methylation in mild cognitively impaired (MCI) older African American (AA) undergoing well-characterized and supervised exercise intervention. Objective of Study: We explored the effects of a six-month aerobic and stretch exercise intervention on the epigenetic modifications and genome-wide DNA methylation of enrolled participants. Twenty-nine older AAs volunteers confirmed to be MCI, were randomly, assigned into a six-month program of either aerobic or stretch exercise. Participants underwent 40 minutes of supervised training 3 times/week. The maximal oxygen consumption (VO2Max) was determined at baseline and repeated after subjects completed the 6-month exercise program. Genome-wide methylation levels at CpG sites from 19 participants at baseline and a 6-month exercise training were profiled by using the Infinium HumanMethylation450 BeadChip assay. We examined the association between the change in CpG sites intensities and VO2 Max after 6 months of exercise adjusting for Age, APOE4 carrier status and randomization group. The participants averaged ∼71 years old in age, were 67.86% female and similar in mean relative VO2 Max (Stretch=24.72 (8.68) vs. Aerobic=22.74 (2.69); p = 0.715) at baseline. In total, we obtained DNA methylation data or 485,513 CpG sites from blood of 19 participants at baseline and after the exercise adaptation. Overall, six CpG sites demonstrated significant training-induced changes in methylation profile: p-values below 5 x 10-5 (cg06648780, cg06120404, cg08733824, cg14318197, cg26580761, cg24583624) with the first two CpG sites located on the ALCAM (leukocyte adhesion molecule) and C1orf88 (primary cilia formation) genes. We provide a genome-wide DNA methylation patterns associated with training-induced changes after a 6-month exercise adaptation. Whereas, efforts to understand the implications of these changes are ongoing, future studies should inform the relationships of changes in DNA methylation to mRNA expression in a predominantly AA sample, and correlate such changes with the MCI clinical phenotype.