We studied the age-dependent regulation of the expression of the antioxidant enzyme manganese superoxide dismutase (MnSOD encoded by Sod2) through promoter methylation. C57Bl/6 mice were either (i) sedentary (SED), (ii) treated with the antioxidant catechin (CAT), or (iii) voluntarily exercised (EX) from weaning (1-month old; mo) to 9 mo. Then, all mice aged sedentarily and were untreated until 12 mo. Sod2 promoter methylation was similar in all groups in 9 mo but decreased (p<0.05) in 12 mo SED mice only, which was associated with an increased (p<0.05) transcriptional activity in vitro. At all ages, femoral artery endothelial function was maintained; this was due to an increased (p<0.05) contribution of eNOS-derived NO in 12 mo SED mice only. CAT and EX prevented these changes in age-related endothelial function. Thus, a ROS-dependent epigenetic positive regulation of Sod2 gene expression likely represents a defense mechanism prolonging eNOS function in aging mouse femoral arteries.
Nguyen, A., Leblond, F., Mamarbachi, M., Geoffroy, S., & Thorin, E. (2016). Age-Dependent Demethylation of Sod2 Promoter in the Mouse Femoral Artery. Oxidative Medicine and Cellular Longevity, 2016. https://doi.org/10.1155/2016/8627384