Age-Dependent Demethylation of Sod2 Promoter in the Mouse Femoral Artery

Abstract EN

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.