肌肉减少症是老年人的主要公共卫生问题,导致残疾,falls,骨折,和死亡率。本研究旨在阐明少肌症的病理生理机制,并使用系统生物学方法确定潜在的治疗靶点。分析了来自先前队列的24个肌少症个体和29个健康个体的肌肉活检的RNA-seq数据。差异表达,基因集富集,基因共表达网络,和拓扑分析进行,以确定与肌肉减少症发病机制有关的靶基因,导致选择6个hub基因(PDHX,AGL,SEMA6C,CASQ1,MYORG,和CCDC69)。然后采用药物再利用方法来确定肌肉减少症的新药物治疗方案(氯纤酸,曲格列酮,在aferin-a中,palbociclib,MG-132,硼替佐米)。最后,在肌肉细胞系(C2C12)中的验证实验显示,MG-132和曲格列酮是治疗肌肉减少症的有希望的候选药物。我们的方法,基于系统生物学和药物重新定位,深入了解肌肉减少症的分子机制,并使用现有药物提供潜在的新治疗选择。
Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, and mortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potential therapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and 29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, gene co-expression network, and topology analyses were conducted to identify target genes implicated in sarcopenia pathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). A drug 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 in muscle 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 mechanisms of sarcopenia and offers potential new treatment options using existing drugs.