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

Abstract

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 (02.-) and hydrogen peroxide (H202) generated by xanthine oxidase and hypoxanthine, or H202 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 02.-and/or H202 to a greater extent in the old rats. Muscle mitochondria from trained young rats showed a greater resistance to the 02 .-and/or H202-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.

Radical Oxygen Species, Exercise and Aging: An Update

“…no change, ; significant decrease Oxidative Stress and Exercise in Elderly Subjects muscle tissue after a training period of 16 weeks at 65 % of VO 2max in older adults (mean age 72.6 ± 1.6 years). This decrease may have been due to greater mitochondrial capacity to scavenge free radicals [116][117][118]. Training may also induce modifications in factors that affect mitochondrial free-radical production.…”

Oxidative stress response and Nrf2 signaling in aging

“…Lu et al found that although SOD2 activity was increased with aging in skin fibroblasts from humans of under 60 years of age, it actually decreased in later years [63]. In contrast, SOD2 activity was reportedly increased in skeletal muscles of humans [66, 78] and rats [70, 86], or not changed [76, 87] with aging.…”

Enhancement of ATP generation capacity, antioxidant activity and immunomodulatory activities by Chinese Yang and Yin tonifying herbs

“…Highly reactive chemically, ROS attack cellular structures located near the sites where ROS are generated. Mitochondrial DNA, proteins, and lipids in the inner membrane of mitochondria are thus vulnerable to oxidative damage [12], resulting in generalized organelle dysfunction, defective mitochondrial biosynthesis and poor energy metabolism [13]. …”