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

The rate of oxidative phosphorylation was investigated in isolated mitochondria 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 of 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-oxoglutarate (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 on state 3 respiration, resulting in a reduction of RCI. Training also increased state 4 respiration with 2-OG and decreased RCI in young rats. When muscle mitochondria were exposed to superoxide radicals (O₂·^-) and hydrogen peroxide (H₂O₂) generated by xanthine oxidase and hypoxanthine, or H₂O₂ alone in vitro, state 3 respiration and RCI in both age groups were 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 by O₂·^- and/or H₂O₂ to a greater extent in the old rats. Muscle mitochondria from trained young rats showed a greater resistance to the O₂·^- and/or H₂O₂-induced state 3 and RCI inhibition than those from untrained young rats. Muscle from aged rats had significantly higher total activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), and glutathione reductase than that from young rats, however, training increased SOD and GPX activities in young but not old rats. The results of this study suggest that mitochondrial capacity for oxidative phosphorylation is compromised in aging skeletal muscle. Further, the increased mitochondrial resistance to reactive oxygen species demonstrated in aged and young trained muscles may be attributed to enhanced antioxidant enzyme activities.