Regulation of SLC7A11 by LncRNA GPRC5D-AS1 mediates ferroptosis in skeletal muscle: Mechanistic exploration of sarcopenia

Sarcopenia is a chronic, progressive disease characterized by the gradual loss of skeletal muscle strength and mass. This study investigates the role of the long non-coding RNA GPRC5D-AS1 in the development and progression of sarcopenia through its regulation of <i>SLC7A11</i>. Skeletal muscle samples were obtained from sarcopenia patients and healthy controls to assess the expression levels of GPRC5D-AS1 and <i>SLC7A11</i>. Flow cytometry was used to evaluate iron content, lipid peroxidation, and antioxidant markers. A ferroptosis model was established in human skeletal muscle cells (HSKM) using the inducer erastin, and GPRC5D-AS1 overexpression plasmids were introduced to observe their effects on cell proliferation and ferroptosis indicators. In the sarcopenia group, both GPRC5D-AS1 and <i>SLC7A11</i> expression levels decreased significantly, along with SLC7A11 protein translation. Erastin treatment markedly reduced cell viability and increased iron content, elevating ferroptosis marker genes (<i>COX2, ACSL4, PTGS2, NOX1</i>) while reducing <i>GPX4</i> and <i>FTH1</i> levels. The overexpression of GPRC5D-AS1 reversed these changes, enhancing antioxidant capacity and cell survival. Conversely, silencing <i>SLC7A11</i> diminished the protective effects of GPRC5D-AS1 on cell proliferation and ferroptosis. These findings suggest that GPRC5D-AS1 overexpression increases <i>SLC7A11</i> expression and reduces ferroptosis incidence in HSKM.