Metabolomic profiles to explore biomarkers of severe sarcopenia in older men: A pilot study

The pathophysiology of sarcopenia is complex and multifactorial; however, it has not yet been fully elucidated. Identifying metabolomic profiles may help clarify the mechanisms underlying sarcopenia.This pilot study explored potential noninvasive biomarkers of severe sarcopenia through metabolomic analysis in community-dwelling older men.Twenty older men (mean age: 81.9 ± 2.8 years) were selected from the Korean Frailty and Aging Cohort Study. Participants with severe sarcopenia (n = 10) were compared with non-sarcopenic, age- and body mass index-matched controls (n = 10). Severe sarcopenia was defined as low muscle mass, low muscle strength, and low physical performance using the Asian Working Group for Sarcopenia 2019 criteria. Non-targeted metabolomic profiling of plasma metabolites was performed using capillary electrophoresis time-of-flight mass spectrometry and absolute quantification was performed in target metabolites.Among 191 plasma metabolic peaks, the concentrations of 10 metabolites significantly differed between severe sarcopenia group and non-sarcopenic controls. The plasma concentrations of L-alanine, homocitrulline, N-acetylserine, gluconic acid, N-acetylalanine, proline, and sulfotyrosine were higher, while those of 4-methyl-2-oxovaleric acid, 3-methyl-2-oxovaleric acid, and tryptophan were lower in participants with severe sarcopenia than in non-sarcopenic controls (all, p < 0.05). Among the 53 metabolites quantified as target metabolites, L-alanine (area under the receiver operating characteristic curve [AUC] = 0.760; p = 0.049), gluconic acid (AUC = 0.800; p = 0.023), proline (AUC = 0.785; p = 0.031), and tryptophan (AUC = 0.800; p = 0.023) determined the presence of severe sarcopenia.Plasma metabolomic analysis demonstrated that L-alanine, gluconic acid, proline, and tryptophan may be potential biomarkers of severe sarcopenia. The identified metabolites can provide new insights into the underlying pathophysiology of severe sarcopenia and serve as the basis for preventive interventions.