Quantitation of oxidative stress and base excision repair in skeletal muscle of high‐ and low‐functioning elderly individuals (863.3)

Skeletal muscle aging is partly attributed to the oxidation of macromolecules caused by increased reactive oxygen species. DNA base excision repair (BER) pathways offer protection against oxidative damage through the removal and repair of DNA lesions. While the activity of these BER enzymes is proposed to be reduced with aging, the molecular details remain elusive. The purpose of this study was to investigate oxidative stress/damage, BER enzyme activities, and antioxidant capacity in skeletal muscle obtained from two sedentary but functionally-distinct groups of elderly (> 65 yr) individuals classified as high- and low-functioning (HF and LF). Results showed increased oxidative damage in both HF and LF individuals compared to young, as indicated by higher levels of 3-Nitrotyrosine (3-NT) and 4-Hydroxynonenal (4-HNE) (P<0.05). This increase corresponded with lower levels of 8-oxoguanine DNA glycosylase (OGG1; P<0.05) protein, the main mitochondrial oxidative DNA repair enzyme, in elderly subjects compared to young. No changes in protein content were observed for apurinic/apyrimidinic (AP) endonuclease, APE1, corresponding to similar rates of AP sites incision when protein extracts from young and elderly individuals were utilized to measure APE1 enzymatic activity. These data suggest that BER capacity may be impaired in aging muscle leading to greater susceptibility to oxidative damage.