T.O.8 Age-dependent effects of angiotensin II blockade on disuse atrophy

Abstract Disuse atrophy is problematic for individuals of all age; however, it is completely reversible in young muscle while aged muscle lacks the ability to recover. Previously we showed that the exaggerated response to disuse atrophy with age is due to a loss of muscle cells as opposed to smaller muscle cells evident in disuse atrophy of young muscle. Here we show that the loss of muscle mass associated with disuse atrophy in adult muscle is due to a combination of a loss of muscle cells and smaller muscle cells. Additionally, the effects of angiotensin II type I receptor blocker (ARB) losartan on disuse atrophy are age-dependent. Losartan confers no protection against disuse atrophy in young mice and partial protection in adult mice. However, it completely protects against the loss of muscle mass in aged mice. The discrepancies in results are due to the modulation of pathways downstream of renin-angiotensin system (RAS), particularly the TGF-β pathway. Additionally, there appears to be age-dependent regulation of the Akt/mTOR/FoxoO3a pathway known to play an integral role in the loss of muscle mass with disuse. These data show that age-related changes occur in response to disuse atrophy and that the changes in the RAS affect the impact of ARBs on the maintenance of skeletal muscle.