A B S T R A C T
Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, andmortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potentialtherapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, geneco-expression network, and topology analyses were conducted to identify target genes implicated in sarcopeniapathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). Adrug repurposing approach was then employed to identify new pharmacological treatment options for sarcopenia(clofibric-acid, troglitazone, withaferin-a, palbociclib, MG-132, bortezomib). Finally, validation experiments inmuscle cell line (C2C12) revealed MG-132 and troglitazone as promising candidates for sarcopenia treatment.Our approach, based on systems biology and drug repositioning, provides insight into the molecular mechanismsof sarcopenia and offers potential new treatment options using existing drugs.
