Identifies metabolite candidates that alleviate muscle atrophy in aging, suggesting metabolic intervention benefits.
Introduction and Objective: Sarcopenia contributes to metabolic dysfunction and physical decline during aging. However, metabolites regulating muscle atrophy remain poorly defined. We aimed to identify metabolite candidates associated with sarcopenia progression and evaluate their effects in muscle atrophy models. Methods: Public skeletal muscle metabolomics datasets across sarcopenia progression were analyzed to identify metabolites showing consistent changes. Candidate metabolites were prioritized using computational annotation. Selected metabolites were tested in differentiated C2C12 myotubes exposed to dexamethasone- or statin-induced atrophic stress, and myotube diameter was quantified. Results: Metabolomics-guided prioritization identified metabolite candidates that progressively declined across stages of sarcopenia. Functional screening in C2C12 myotubes showed that several candidates partially restored myotube diameter under glucocorticoid- or statin-induced atrophic conditions (Fig.1). Additional in vitro and in vivo studies are currently underway to further evaluate candidate metabolites and their mechanisms of action. Conclusion: These findings identify metabolite candidates associated with sarcopenia progression and suggest that metabolic modulation may attenuate skeletal muscle atrophy and support muscle metabolic resilience. Disclosure S. Park: None. B. Lee: None. Funding National Research Foundation of Korea (RS-2021-NR060118), National Research Foundation of Korea (RS-2023-00274576), Ministry of Oceans and Fisheries (RS-2025-02373103)
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