Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China.
Bioengineered. 2021 Dec;12(1):3485-3502. doi: 10.1080/21655979.2021.1948951.
Age-related skeletal muscle deterioration (sarcopenia) has a significant effect on the elderly's health and quality of life, but the molecular and gene regulatory mechanisms remain largely unknown. It is necessary to identify the candidate genes related to skeletal muscle aging and prospective therapeutic targets for effective treatments. The age-line-related genes (ALRGs) and age-line-related transcripts (ALRTs) were investigated using the gene expression profiles of GSE47881 and GSE118825 from the Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) networks were performed to identify the key molecules with Cytoscape, and Gene Set Enrichment Analysis (GSEA) was used to clarify the potential molecular functions. Two hub molecules were finally obtained and verified with quantitative real-time PCR (qRT-PCR). The results showed that the expression of mitochondria genes involved in mitochondrial electron transport, complex assembly of the respiratory chain, tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis were down-regulated in skeletal muscle with aging. We further identified a primary hub gene of CYCS (Cytochrome C) and a key transcription factor of ESRRA (Estrogen-related Receptor Alpha) to be associated closely with skeletal muscle aging. PCR analysis confirmed the expressions of CYCS and ESRRA in gastrocnemius muscles of mice of different ages were significantly different, and decreased gradually with age. In conclusion, the main cause of skeletal muscle aging may be the systematically reduced expression of mitochondrial functional genes. The CYCS and ESRRA may play significant roles in the progression of skeletal muscle aging and serve as potential biomarkers for future diagnosis and treatment.
年龄相关性骨骼肌衰减症（肌少症）对老年人的健康和生活质量有重大影响，但分子和基因调控机制在很大程度上仍不清楚。有必要确定与骨骼肌衰老相关的候选基因和有前途的治疗靶点，以实现有效的治疗。本研究利用基因表达综合数据库（GEO）中 GSE47881 和 GSE118825 数据集的基因表达谱，对年龄相关基因（ALRGs）和年龄相关转录本（ALRTs）进行了研究。使用 Cytoscape 构建蛋白质-蛋白质相互作用（PPI）网络，以确定关键分子，并用基因集富集分析（GSEA）来阐明潜在的分子功能。最后通过定量实时 PCR（qRT-PCR）验证了两个关键基因。结果表明，衰老骨骼肌中线粒体基因的表达下调，涉及线粒体电子传递、呼吸链复合物组装、三羧酸循环、氧化磷酸化和 ATP 合成。我们进一步确定了 CYCS（细胞色素 C）的主要核心基因和 ESRRA（雌激素相关受体-α）的关键转录因子与骨骼肌衰老密切相关。PCR 分析证实，不同年龄组小鼠腓肠肌中 CYCS 和 ESRRA 的表达存在显著差异，且随年龄逐渐降低。总之，骨骼肌衰老的主要原因可能是线粒体功能基因的系统性低表达。CYCS 和 ESRRA 可能在骨骼肌衰老的进展中发挥重要作用，可作为未来诊断和治疗的潜在生物标志物。
