Circulating Biomarkers of the Brain–muscle–metabolic Axis in Primary Sarcopenia: Neudesin, Nesfatin-1, and Irisin

Circulating neudesin, nesfatin-1, and irisin levels were measured in older adults with primary sarcopenia, and their diagnostic value was evaluated. Older adults with sarcopenia exhibited significantly lower serum concentrations of neudesin, nesfatin-1, and irisin. After adjustment for body mass index (BMI), neudesin and nesfatin-1 remained independently associated with sarcopenia, while the association with irisin was attenuated. All three biomarkers demonstrated good discriminatory ability for identifying sarcopenia. The results support the hypothesis that sarcopenia is characterized by dysregulation of the brain–muscle–metabolic axis, in addition to muscle loss. Circulating biomarkers may contribute to future risk stratification strategies. However, larger prospective studies are required before clinical application. Sarcopenia is an age-related geriatric syndrome characterized by the progressive loss of skeletal muscle mass, strength, and physical performance. Although muscle-based assessments remain central to diagnosis, no specific circulating biomarker is currently available for early detection. Emerging evidence suggests that neudesin, nesfatin-1, and irisin are involved in muscle metabolism, energy homeostasis, and the regulation of inflammation. This study aimed to investigate the association of these biomarkers with primary sarcopenia in older adults and to evaluate their potential diagnostic utility. This study included 88 participants aged ≥ 65 years (58 women, 30 men), excluding secondary sarcopenia. Diagnosis was based on EWGSOP2 criteria. Serum neudesin, nesfatin-1, and irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). Sociodemographic characteristics, comorbidities, medication use, anthropometric parameters, and comprehensive geriatric assessment data were collected. Serum concentrations of neudesin, nesfatin-1, and irisin were significantly lower in individuals with sarcopenia compared to non-sarcopenic controls (p = 0.001, p < 0.001, and p < 0.001, respectively). After adjustment for body mass index (BMI), neudesin and nesfatin-1 remained independently associated with sarcopenia, whereas the association between irisin and sarcopenia was attenuated. All three biomarkers demonstrated good discriminatory ability for sarcopenia. Reduced serum concentrations of neudesin, nesfatin-1, and irisin are significantly associated with primary sarcopenia in older adults. Nesfatin-1 and neudesin appear to be the most robust biomarker candidates, independent of adiposity. These results suggest that sarcopenia involves alterations in interconnected metabolic, endocrine, and neurotrophic pathways within the brain–muscle–metabolic axis. This study is the first to evaluate a combined neurotrophic, myokine, and metabolic biomarker panel in primary sarcopenia. Additional prospective studies are necessary to validate these findings and determine their clinical relevance.