Experimental Research On The Mechanism Of Exercise Intervention To Age-related Muscle Atrophy

Age-related muscle atrophy refers to the decline in muscle mass and strength with advancing age, which results in the increased risk of fall and fracture in the elderly, and the decreased ability of daily activities. With the increasing elderly population, research on age-related muscle atrophy has become a hot issue in recent years, more understanding of its pathogenesis and intervention strategies should be of significance. Due to the complication of the mechanisms, there was still lack of highly targeted and effective method of treatment, intervention or even reversal to this type of muscle atrophy up to date. Exercise has been suggested as a key factor to enhance the structure and function of skeletal muscle and an effective method delay aging. But endurance exercise or resistance exercise may interfere with age-related muscle atrophy by distinct mechanisms, and its interventional effects may also be different. We hypothesisd that the combination of endurance exercise and resistance exercise might play a more prominent role in intervention to aged muscle.The article focused primarily on the intervention effects and its mechanisms of different types of exercise such as endurance exercise, resistance exercise, or combined exercise in age-related muscle atrophy, including the level of oxidative stress, the phosphorylated level of signaling kinases and mitochondrial function, to explore the best exercise intervention.Eighteen-month-old female KM mice were assigned to undergo endurance training, resistance training, or combined training for 10-12 weeks, respectively. Within 1-2 days at end of training, mice were sacrificed in rest state, then rectus femoris and gastrocnemius were collected quikly, weighed, frozen in liquid nitrogen at -80℃. The content of MDA, the activity of anti-oxidant enzyme SOD, CAT, and GPX were measured by biochemical assays. The phosphorylation levels of protein kinases mTOR, p70S6K, ERK1/2 were analysized by Western blotting. The deletion mutant rates of mtDNA were determined by PCR, the activity of mitochondrial complexⅠ,Ⅲ,Ⅳwere measured by biochemical methods. SPSS11.5 statistical software package was used for multi-factor analysis of variance and multi-comparation, significance level was set at P<0.05.The results in the present study showed that with advancing age, the muscle mass of the rectus femoris and gastrocnemius decreased significantly. The MDA content and GPX activity increased in aged skeletal muscle tissue, while SOD activity and CAT activity decreased significantly. In addition, The phosphorylation levels of protein kinases mTOR, p70S6K, ERK1/2 decreased in aged mice. The deletion mutation rate of mitochondrial (mtDNA%) was higher in aged mice compared with controls, while the activity of mitochondrial complexⅠ,Ⅲ,Ⅳdecreased. Therefore, elevated levels of oxidative stress, and decreased signaling kinase activity of protein synthesis, and mitochondrial dyfunction may be cellular and molecular mechanism of age-related muscle atrophy.Moreover, there was an significant increase in muscle mass of the rectus femoris and gastrocnemius from aged mice after resistance exercise and combined exercise, but no marked effect from aged mice after endurance exercise.After endurance exercise, there were significant decrease in MDA content, and increase in SOD, CAT and GPX activity in the gastrocnemius muscle of aged mouse. After resistance exercise, GPX activity significantly increased, while MDA content, SOD, and CAT activity didn't change. By combined exercise, MDA content in the gastrocnemius muscle of aged mice significantly decreased, SOD, CAT and GPX activity were significantly higher. The phosphyorylation levels of mTOR, p70S6K and ERK1/2 kinases in aged mice were enhanced significantly by resistance exercise and combined exercise. However, there was no significant increase in phosphorylated mTOR, p70s6k after endurance exercise in aged mice compared with controls.Through different types of exercise training interventions, the rate of mitochondrial deletion and oxidative damage were reduced significantly in muscles of aging model. Resistance exercise significantly increased the activity of complexⅠ,Ⅲ,Ⅳin the rectus femoris muscle of aged mice. Combined exercise markedly improved the activity of complexⅠ,Ⅳin aging mice rectus femoris muscle. However, endurance exercise did not significantly improve the complexⅠ,Ⅲ,Ⅳactivity in aged muscle.It had been shown in the present study, that the intervention effects and related mechanisms of different types of exercise training including endurance training, resistance training, combined training on age-related muscle atrophy were obviously different. Endurance training enhanced the antioxidant capacity of aged muscle and mitochondrial function, but did not induce increased muscle mass. Resistance exercise not only induced muscle hypertrophy, increased protein synthesis activity of signaling molecules, reversd age-related muscle mass decline, but also enhanced mitochondrial function. Combination of exercise also improved the status of oxidative stress, enhanced the ability of protein synthesis, and induced muscle mass growth in aged mice. Combined exercise has more comprehensive effects of intervention to age-related muscle atrophy.Further research on the mechanisms of age-related muscle atrophy needs to be performed. Based on these researches, the best strategy for the future is to develop effective combined interventions to age-related muscle atrophy.