A possible role of sclerostin in aging-associated skeletal muscle atrophy

Maintaining skeletal muscle function, as well as preventing and treating sarcopenia, is important for extending a healthy lifespan. Serum sclerostin (SOST) levels increase with age and inhibit bone formation by blocking Wnt/β-catenin signaling. Recent evidence indicates that SOST inhibits skeletal muscle differentiation; therefore, SOST may be involved in age-related skeletal muscle atrophy. In this study, we investigated SOST expression levels in human skeletal muscles with sarcopenia and the effects of an anti-SOST antibody romosozumab (ROMO) on gastrocnemius muscles of ovariectomized sarcopenia-model mice. In human experiments, the gluteus maximus muscle was collected from patients with or without sarcopenia who were undergoing surgery for proximal femoral fractures. SOST and β-catenin in the gluteus maximus muscle were compared between patients with and without sarcopenia. In the animal experiments, 8-week-old mice were used. The control (Cont) group was maintained under normal conditions, while the ovariectomized (OVX) group was ovariectomized and maintained under normal conditions for 15 weeks. The ROMO-treated (ROMO) group underwent the same treatment as the OVX group and then received two doses of ROMO at 3 mg/kg, four weeks apart. Four weeks after the final ROMO administration, the gastrocnemius muscles were collected from each group. Body weight, muscle wet weight, muscle fiber cross-sectional area (fCSA), and the intramuscular expression levels of SOST and β-catenin. were analyzed. The significance level was set at 5%. Expression levels of SOST in human gluteus maximus muscle were significantly higher in the OVX group. Conversely, β-catenin expression levels were significantly lower in the OVX group. In animal experiments, the body weight was significantly higher in the OVX group than in the Cont and ROMO groups. Muscle wet weight and muscle fCSA were significantly lower in the OVX group than in the Cont and ROMO groups. SOST expression in the gastrocnemius muscle was significantly higher in the OVX group than in the control and ROMO groups. β-catenin expression was significantly lower in the OVX group than in the Cont and ROMO groups. Results indicate that SOST is involved in sarcopenia. Administration of ROMO may suppress skeletal muscle atrophy caused by OVX. Taken together, these results demonstrate the potential of ROMO for suppressing aging-associated skeletal muscle atrophy. This work was supported by KAKENHI (18H03160, KG; 19K22825, KG; 19KK0254, KG; 22H03474, KG; 22K19722, KG; 22H03319, KG; 22K18413, KG; 20K11221, TK; 25K14392, TK) from the Japan Society for the Promotion of Science, and a grant from DAIKO FOUNDATION (KG), Graduate School of Health Science, Toyohashi SOZO University (KG), and a research grant from Toyohashi SOZO university (KG). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.