Computational analysis of hub genes associated with sarcopenia: integrative transcriptome insights from an Asian cohort

Sarcopenia, a progressive loss of skeletal muscle mass and strength, leads to frailty, falls, fractures, and delayed recovery following orthopedic surgery. When combined with osteoporosis, it manifests as osteosarcopenia, exacerbating musculoskeletal fragility. Although chronic inflammation, mitochondrial dysfunction, and impaired autophagy are recognized contributors, the integrated regulation of these processes in Asian populations remains unclear. This study aimed to elucidate molecular mediators and signaling pathways connecting inflammation, autophagy, and muscle-bone degeneration using an integrated clinical-transcriptomic approach. Transcriptomic data (GSE226151) comprising vastus lateralis muscle samples from 20 sarcopenic patients and 20 age- and sex-matched healthy Asian controls were analyzed using ExDEGA, with differentially expressed genes (DEGs) defined by |log₂ fold change| ≥ 1 and FDR < 0.05. Functional enrichment via ShinyGO identified key Gene Ontology and KEGG pathways, while STRING–Cytoscape network analysis revealed four hub genes—ADAM8, BECN1, KLF4, and GBP5—with high connectivity (degree >10) enriched in cytokine–cytokine receptor interaction and PI3K–Akt pathways. Gene Set Enrichment Analysis further validated these associations. The expression of these hub genes inversely correlated with skeletal muscle index (r = –0.63 to –0.74; p < 0.01) and grip strength (r = –0.58 to –0.69; p < 0.05). Clinically, sarcopenic individuals exhibited significantly lower BMI, gait speed, and muscle mass (all p < 0.001). Integrating bioinformatics and clinical data identified these four genes as critical mediators linking inflammation, defective autophagy, and musculoskeletal decline in sarcopenia. These findings provide translational insight into the molecular mechanisms underlying osteosarcopenia and suggest potential biomarkers and therapeutic targets to improve diagnosis and treatment in aging-related musculoskeletal disorders.