Oxidative stress and mitochondrial function in skeletal muscle: Effects ofaging and exercise training

The rate of oxidative phosphorylation was investigated in isolated mitochon dria from hindlimb muscles of young (4.5 mo) and old (26.5 mo) male Fischer 344 rats with or without endurance training. Further, the susceptibility o f the muscle mitochondria to exogenous reactive oxygen species was examined . State 3 and 4 respiration, as well as the respiratory control index (RCI) , were significantly lower in muscle mitochondria from aged vs. young rats (P<0.05), using either the site 1 substrates malate-pyruvate (M-P) and 2-ox oglutarate (2-OG), or the site 2 substrate succinate. In both young and old rats, training increased state 4 respiration with M-P, but had no effect o n state 3 respiration, resulting in a reduction of RCI. Training also incre ased state 4 respiration with 2-OG and decreased RCI in young vats. When mu scle mitochondria were exposed to superoxide radicals (O-2 radical anion ) and hydrogen peroxide (H2O2) generated by xanthine oxidase and hypoxanthine , or H2O2 alone in vitro, state 3 respiration and RCI in both age groups we re severely hampered, but those from the old rats were inhibited to a less extent than the young rats. In contrast, state 4 respiration was impaired b y O-2 radical anion and/or H2O2 to a greater extent in the old rats. Muscle mitochondria from trained young rats showed a greater resistance to the O- 2 radical anion and/or H2O2-induced state 3 and RCI inhibition than those f rom untrained young rats. Muscle from aged rats had significantly higher to tal activities of superoxide dismutase (SOD), catalase, glutathione peroxid ase (GPX), and glutathione reductase than that from young rats, however, tr aining increased SOD and GPX activities in young but not old rats. The resu lts of this study suggest that mitochondrial capacity for oxidative phospho rylation is compromised in aging skeletal muscle. Further, the increased mi tochondrial resistance to reactive oxygen species demonstrated in aged and young trained muscles may be attributed to enhanced antioxidant enzyme acti vities.