Aging Augments Oxidative Stress In Skeletal Muscle During Suspension-induced Unloading

Abstract

Oxidative stress increases during hindlimb suspension in muscle from young adult animals. However, it is not known if oxidative stress is also increased in a similar fashion during unloading in aged skeletal muscle. Therefore, the PURPOSE of this study was to test the hypothesis that aging augments oxidative stress during muscle unloading-induced atrophy. METHODS: By using the techniques of RT-PCR, western immunobloting and other biochemical assays, the present study examined the markers of oxidative stress and antioxidant enzymes gene and protein expressions in gastrocnemius muscles of young adult and aged Fischer344xBrown Norway rats after 14 days of hindlimb suspension. RESULTS: Sarcopenia was observed when comparing both muscle wet weights and muscle weight normalized to body weight between young adult and aged animals. As expected, muscle mass decreased after suspension in both young adult and aged animals. The contents of MDA/4-HAE and nitrotyrosine and the catalase activity were greater in unloaded relative to control muscles in young adult and aged animals. H2O2 content was elevated while MnSOD protein content was reduced in suspended muscles when compared to control muscles exclusively in the aged animals. Changes in oxidative stress markers MDA/4-HAE, H2O2 and MnSOD protein contents to hindlimb unloading occurred in an age-dependent manner. The age-related decrease in muscle mass was accompanied by greater catalase activity and contents of H2O2, 8-OHdG and nitrotyrosine but lower abundances of MnSOD mRNA and protein and catalase mRNA, relative to muscles from young adult animals. CONCLUSIONS: These findings are consistent with the hypotheses that oxidative stress has a role in mediating disuse-induced and sarcopenia associated muscle losses. Our data suggest that aging may predispose skeletal muscle to increased levels of oxidative stress both at rest and during unloading.