Aerobic exercise attenuates sarcopenia-related changes via TXNIP-associated modulation of apoptosis, inflammation and autophagy.

Sarcopenia is an age-related syndrome characterized by progressive loss of skeletal muscle mass, strength, and function, and represents a major challenge to healthy aging. Thioredoxin-interacting protein (TXNIP) has been associated with skeletal muscle alterations in sarcopenia, but its potential role in exercise-related adaptation remains unclear. In this study, naturally aged male Sprague-Dawley rats underwent a 10-week treadmill exercise intervention, and gastrocnemius muscle was examined using morphological, functional, and molecular approaches. Aging was associated with reduced relative gastrocnemius muscle mass, smaller myofiber cross-sectional area, impaired grip strength and endurance capacity, increased Atrogin-1 and MuRF-1 expression, enhanced apoptosis- and inflammation-related signaling, reduced Trx expression, increased TXNIP protein expression, detectable TXNIP-Trx and TXNIP-NLRP3 interactions, and altered autophagy-related markers. Aerobic exercise improved muscle morphology and endurance-related performance in aged rats, and was accompanied by reduced Atrogin-1 and MuRF-1 expression, coordinated changes in apoptosis-, inflammation-, and autophagy-related markers, reduced TXNIP expression at both mRNA and protein levels, decreased TXNIP-Trx and TXNIP-NLRP3 interactions, and altered PI3K/Akt/mTOR-related protein phosphorylation. These findings suggest that aerobic exercise may attenuate sarcopenia-related changes in aged skeletal muscle, potentially in association with TXNIP-related multi-pathway regulation.