1783-P: HM17321, a CRFR2 Selective UCN2 Analog, Prevents Muscle Loss and Functional Decline in Sarcopenic Mice
Abstract
Introduction and Objective: Sarcopenia is characterized by progressive deterioration of skeletal muscle mass, structural integrity and function. Senescence-accelerated mouse-prone 8 (SAMP8) mice represent accelerated aging model that recapitulates key features of sarcopenia. HM17321 is a CRFR2-selective UCN2 analog with established metabolic benefits and emerging relevance to skeletal muscle health. This study evaluated the effects of HM17321 on aging-associated sarcopenia in SAMP8 mice and its efficacy across complementary models of muscle atrophy.
Methods: Male SAMP8 mice were subcutaneously administrated with HM17321 for 4 months, with senescence-resistant SAMR1 mice as age-matched controls. Body composition, neuromuscular function and aging-associated pheontypes were longitudinally assessed. Skeletal muscle atrophy was evaluated by histological analysis. The efficacy of HM17321 against muscle wasting was further assessed in a dexamethasone-induced muscle atrophy model.
Results: Relative to SAMR1 mice, SAMP8 mice exhibited accelerated skeletal muscle degeneration and function decline. HM17321 broadly ameliorated these age-associated deficits, increasing lean mass (up to +7.9% vs. SAMP8 vehicle) while reducing fat mass (up to -23.0%), with concomitant enhancements in muscle performance, including grip strength and holding impulse, as well as attenuation of kyphosis and hindlimb clasping. These improvements were supported by preserved muscle architecture, with maintained…
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