SENSITIVITY AND PROTEIN-TURNOVER RESPONSE TO GLUCOCORTICOIDS ARE DIFFERENT IN SKELETAL-MUSCLE FROM ADULT AND OLD RATS - LACK OF REGULATION OF THE UBIQUITIN-PROTEASOME PROTEOLYTIC PATHWAY IN AGING

We studied glucocorticoid-induced muscle wasting and subsequent recove ry in adult (7-mo-old) and old (22-mo-old) rats, since the increased i ncidence of various disease states may result in glucocorticoids hyper secretion in aging, Adult and old rats received dexamethasone in their drinking water and were then allowed to recover, Muscle wasting occur red more rapidly in old rats and the recovery of muscle mass was impai red, suggesting that glucocorticoids may be involved in the emergence of muscle atrophy with advancing age. According to measurements in inc ubated epitrochlearis muscles, dexamethasone-induced muscle wasting ma inly resulted from increased protein breakdown in the adult, but from depressed protein synthesis in the aged animal, Increased expression o f cathepsin D, m-calpain, and ubiquitin was observed in the muscles fr om both dexamethasone-treated adult and old rats, By contrast, the dis appearance of the stimulatory effect of glucocorticoids on protein bre akdown in aging occurred along with a loss of ability of steroids to e nhance the expression of the 14-kD ubiquitin carrier protein E2, which is involved in protein substrates ubiquitinylation, and of subunits o f the 20 S proteasome (the proteolytic core of the 26 S proteasome tha t degrades ubiquitin conjugates). Thus, if glucocorticoids play any ro le in the progressive muscle atrophy seen in aging, this is unlikely t o result from an activation of the ubiquitin-proteasome proteolytic pa thway.