Abstract
BACKGROUND: Sarcopenia is the progressive, widespread loss of skeletal muscle mass, strength, and function, which happens as a result of aging. This study aims to analyze the alterations in serum protein profiles and explore a biomarker of diagnostic significance for early sarcopenia patients via a cross-sectional study. METHODS: In this cross-sectional study, serum samples from 50 older adults (25 with early sarcopenia and 25 healthy controls) were analyzed. In the discovery cohort (10 per group), proteomic sequencing was performed to identify differentially expressed proteins (DEPs). Candidate biomarker were subsequently validated using enzyme-linked immunosorbent assay (ELISA) in an independent validation cohort (15 per group). Furthermore, bioinformatics analyses, including functional enrichment and diagnostic evaluation, were conducted to elucidate the potential role of the identified targets. RESULTS: Untargeted proteomic profiling of the discovery cohort identified 88 significantly dysregulated serum proteins in early sarcopenia, which were bioinformatically enriched in processes related to stress response and metabolic imbalance. To prioritize candidate biomarkers, the corresponding genes were cross-referenced with public transcriptomic data. This integrative analysis highlighted apolipoprotein D (APOD) as a leading candidate gene, demonstrating concurrent upregulation at both the proteomic and transcriptomic levels and exhibiting strong diagnostic potential (area under the curve (AUC) > 0.7). The specific elevation of serum APOD protein was subsequently confirmed through orthogonal validation via ELISA in an independent cohort, where its levels were significantly higher in patients with early sarcopenia compared to healthy controls. Furthermore, gene set enrichment analysis implicated APOD in the modulation of key pathways, including the activation of the PI3K-Akt signaling pathway and the suppression of pathways related to cardiovascular function, suggesting its potential role in the metabolic dysregulation characteristic of early muscle decline. CONCLUSION: This study identifies and validates serum APOD as a biomarker associated with early sarcopenia, characterized by significantly elevated levels and demonstrating promising discriminative capacity at the group level between affected individuals and healthy controls.