Moderate intensity aerobic exercise prevents myopathic consequences of glucocorticoid administration in aged female mice

Abstract

Elevated glucocorticoids induce a myopathy characterized by the loss of muscle mass and increased muscle fatiguability. The elderly is highly susceptible to the myopathic effects as they are more likely to experience elevated glucocorticoid levels. Aerobic exercise can prevent glucocorticoid-induced loss of muscle in younger rodents; however, it is unknown whether aerobic exercise can influence glucocorticoid myopathic features in aged muscle. Therefore, the purpose of this study was to define the extent to which moderate intensity aerobic exercise influenced glucocorticoid myopathy in aged muscle. 24-month-old female C57BL/6 mice were randomized into 4 groups of equal bodyweights. Two groups remained sedentary while the other 2 groups began treadmill aerobic exercise performed 5x/week at 10 m/min for 30 min at 5% grade. At the end of the first week of exercise, one group of sedentary mice and one group of exercising mice began receiving once daily subcutaneous injections of dexamethasone (1 mg/kg; DEX). The other group of sedentary mice and group of exercising mice began receiving once daily subcutaneous injections of saline only. All treatments (sedentary/exercise or DEX/saline) continued for an additional 2 weeks. At the end of week 3, the contractile properties of the triceps surae muscle complex were assessed in situ via electrical stimulation of the sciatic nerve. Specific measures included twitch force, sub tetanic force (60 Hz stimulation frequency), tetanic force (125 Hz stimulation frequency), and a fatigue protocol consisting of 60 high force contractions, with each contraction separated by 4 seconds. After testing, muscles of the triceps surae complex were extracted and weighed. Total protein content of the gastrocnemius was determined by the Bradford method. DEX lowered muscle mass, lowered gastrocnemius total protein content, and enhanced fatigue, with aerobic exercise preventing those changes. Interestingly, main effects were noted for DEX to increase twitch and 60 Hz absolute force, normalized force, and RFD in both sedentary and exercise trained mice. Neither DEX nor exercise altered half-relaxation time at any stimulation frequency, nor did they alter tetanic force at the 125 Hz stimulation. These data show that the detrimental effects of elevated glucocorticoids to skeletal muscle morphology and contractile function in aged muscle can be mitigated by moderate intensity aerobic exercise training. They also indicate that there may be some positive benefits to submaximal force generating capacity following a clinically relevant dose of glucocorticoids in aged females. This work was supported by a Doctoral grant from the American College of Sports Medicine (GRL) and NIH R03AG073445 (BSG). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.