Amino acid metabolites as potential circulating biomarkers for sarcopenia

Sarcopenia, characterized by the loss of muscle mass and strength, is a multifactorial disorder, including metabolic disturbance. Plasma amino acids (AAs) regulate muscle protein synthesis and breakdown. This study evaluated plasma AA metabolites as potential biomarkers for sarcopenia using metabolomic analysis. We assessed 31 AA metabo lites in an age-matched discovery cohort (72 men, 36 women with sarcopenia; 72 and 36 controls) and a validation cohort (36 men, 46 women with sarcopenia; 128 and 112 controls). In discovery cohort, isoleucine (Ile), leucine (Leu), valine (Val), methionine (Met), phenylalanine (Phe), tryptophan (Trp), alpha-aminoadipic acid (alpha-AAA), glutamate (Glu), and methionine sulfoxide (MetO) were lower in men with sarcopenia, while Glu was lower in women (p < 0.05). Leu in men and Glu in both sexes were associated with skeletal muscle index. A regression model combining Leu and Glu in men and Glu in women yielded an AA score. Adding the AA score to hand grip strength improved the area under the receiver-operating characteristic curve in men (0.646 to 0.767, p = 0.003; 0.563 to 0.767, p = 0.002) and in women (0.486 to 0.728, p < 0.001; 0.576 to 0.680, p = 0.018). Leu in men and Glu in both sexes, reflecting low muscle mass, are potential circulating biomarkers for sarcopenia.