Metabolite biomarkers present in urine predict alterations in skeletal muscle associated with sarcopenia

Introduction: Sarcopenia, characterized by the progressive loss of skeletal muscle mass and strength with age, is associated with adverse health outcomes and reduced health span in aging populations. Early detection is critical for implementing preventive strategies; however, current diagnostic methods are often costly, specialized, and not suitable for routine screening. This study aimed to identify metabolite biomarkers associated with early alterations in muscle metabolism that may support accessible screening approaches. Methods: In this cross-sectional observational study, serum samples from 200 individuals aged 550-70 years from the general population were analyzed. Participants completed the International Physical Activity Questionnaire (IPAQ). In a subset of 60 participants, urine samples were also collected, and participants underwent additional assessments including the Short Physical Performance Battery (SPPB), dual-energy X-ray absorptiometry (DXA), IPAQ, and a supplementary health questionnaire. Targeted metabolomic analyses were performed to identify metabolites associated with early sarcopenia-related metabolic changes. Results: A panel of metabolites in serum-L-glutamic acid, xanthine, taurine, succinate, and L-carnitine-was associated with early alterations in muscle metabolism. These metabolites were also detectable in urine samples. Importantly, predictive performance for sarcopenia-related changes was observed when the metabolites were analyzed as a combined panel rather than as individual biomarkers. Conclusion: Our findings identify a metabolite panel detectable in urine that reflect early metabolic alterations associated with sarcopenia. This panel provide a foundation for developing accessible screening tools to support early detection and preventive strategies for muscle health decline in aging populations.