We found that (i) SELENOW KO aggravated muscle mass loss in dexamethasone (DEX)–induced muscle atrophy and age-related sarcopenia mouse models; (ii) SELENOW KO disrupted the balance of protein synthesis and degradation in skeletal muscle through the RAC1-mTOR cascade; and (iii) overexpression of SELENOW alleviated DEX-induced muscle and myotube atrophy in in vivo and in vitro studies. Here, MTOR is linked to sarcopenia.