PR002377 (Project)

Description:Disused muscle atrophy (DMA) is a debilitating condition characterized by progressive skeletal muscle loss and functional decline due to prolonged inactivity, such as immobilization or microgravity. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been implicated in DMA, but its precise role remains unclear. The xCT-GSH-GPX4 axis serves as a critical defense against ferroptosis, while the AMPK-ACC-ACSL4 pathway regulates ferroptosis susceptibility through lipid metabolism. Taurine, a naturally occurring amino acid, has been shown to act as a nutritional supplement and ferroptosis inhibitor protecting the proliferation and myogenic differentiation potential of myoblasts. In this study, we investigated the role of ferroptosis in DMA and the therapeutic potential of taurine using a hindlimb suspension-induced DMA mouse model. Our results showed that DMA induced significant muscle atrophy and ferroptosis-related abnormalities, including decreased muscle mass and function, excessive iron accumulation, increased malondialdehyde levels, and decreased GSH levels and xCT expression. Taurine supplementation effectively attenuated these pathological changes, confirming ferroptosis as a key driver of DMA and taurine alleviated DMA through inhibiting ferroptosis. Mechanistically, taurine activated the xCT-GSH-GPX4 and AMPK-ACC-ACSL4 pathways, promoting GSH synthesis, enhancing oxidative defenses, suppressing fatty acid synthesis, and reducing lipid peroxidation. These findings establish a critical link between ferroptosis and DMA, underscore the therapeutic potential of taurine in muscle preservation, and provide new insights into the prevention and treatment of DMA through ferroptosis-targeted strategies.