Short‐term aerobic exercise prevents development of glucocorticoid myopathic features in aged skeletal muscle in a sex‐dependent manner

Older adults are vulnerable to glucocorticoid‐induced muscle atrophy and weakness, with sex potentially influencing their susceptibility to those effects. Aerobic exercise can reduce glucocorticoid‐induced muscle atrophy in young rodents. However, it is unknown whether aerobic exercise can prevent glucocorticoid myopathy in aged muscle. The objectives of this study were to define the extent to which sex influences the development of glucocorticoid myopathy in aged muscle, and to determine the extent to which aerobic exercise training protects against myopathy development. Twenty‐four‐month‐old female (n = 30) and male (n = 33) mice were randomized to either sedentary or aerobic exercise groups. Within their respective groups, mice were randomized to either daily treatment with dexamethasone (DEX) or saline. Upon completing treatments, the contractile properties of the triceps surae complex were assessed in situ. DEX marginally lowered muscle mass and soluble protein content in both sexes, which was attenuated by aerobic exercise only in females. DEX increased sub‐tetanic force and rate of force development only in females, which was not influenced by aerobic exercise. Muscle fatigue was higher in both sexes following DEX, but aerobic exercise prevented fatigue induction only in females. The sex‐specific differences to muscle function in response to DEX treatment coincided with sex‐specific changes to the content of proteins related to calcium handling, mitochondrial quality control, reactive oxygen species production, and glucocorticoid receptor in muscle. These findings define several important sexually dimorphic changes to aged skeletal muscle physiology in response to glucocorticoid treatment and define the capacity of short‐term aerobic exercise to protect against those changes. Key points There are sexually dimorphic effects of glucocorticoids on aged skeletal muscle physiology. Glucocorticoid‐induced changes to aged muscle contractile properties coincide with sex‐specific differences in the content of calcium handling proteins. Aerobic exercise prevents glucocorticoid‐induced fatigue only in aged females and coincides with differences in the content of mitochondrial quality control proteins and glucocorticoid receptors. figure legend Daily 1 mg/kg dexamethasone (DEX) treatment in 24‐month‐old female and male mice results in sexually dimorphic effects on skeletal muscle physiology. Short‐term treadmill exercise mitigates the DEX‐induced myopathic feat