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Background: Sarcopenia is a clinical syndrome characterized by continuous loss of skeletal muscle mass, muscle strength or function. Sarcopenia, which increases the risk of falls and fractures, is also closely associated with metabolic diseases and cognitive dysfunction, resulting in serious adverse effects on people’s quality of life and inflicting a heavy socio-economic burden. In the present study, we aim to identify potential crucial genes associated with sarcopenia through bioinformatic analyses of public datasets.Methods: The gene expression profiles (GSE1428) were downloaded from the Gene Expression Omnibus (GEO) database. The difference expression genes (DEGs) between sarcopenia samples and normal samples were screened. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Protein-protein interaction (PPI) network was constructed using the STRING database. Cytoscape with CytoHubba were used to identify the hub genes.Results: Totally, 314 up-regulated genes and 289 own-regulated genes were identified. In addition, the most significantly enriched pathway was Cell cycle, Human T-cell leukemia virus 1 infection, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, Signaling pathways regulating pluripotency of stem cells. In combination with the results of the protein–protein interaction (PPI) network and CytoHubba, 10 hub genes including CD4、PLK1、CHEK2、LCP2、NANOG、PTPN11、RUNX2、ANXA5、BUB1B、CCR5 were selected. Conclusions: The 10 potential crucial genes may be associated with risk of sarcopenia. Our study provided new insights of sarcopenia into genetics, molecular pathogenesis and new therapeutic targets. It also will contribute to identification of potential biomarkers and novel strategies for sarcopenia.

Activation of the proinflammatory-associated cytokine, tumor necrosis factor-α (TNF-α), in nucleus pulposus (NP) cells is essential for the pathogenesis of intervertebral disc degeneration (IDD). Restoring autophagic flux has been shown to effectively protect against IDD and is a potential target for treatment. The goal of this study was to explore particular autophagic signalings responsible for the protective effects of naringin, a known autophagy activator, on human NP cells. The results showed that significantly increased autophagic flux was observed in NP cells treated with naringin, with pronounced decreases in the inflammatory response and oxidative stress, which rescued the disturbed cellular homeostasis induced by TNF-α activation. Autophagic flux inhibition was detectable in NP cells cotreated with 3-methyladenine (3-MA, an autophagy inhibitor), partially offsetting naringin-induced beneficial effects. Naringin promoted the expressions of autophagy-associated markers via SIRT1 (silent information regulator-1) activation by AMPK (AMP-activated protein kinase) phosphorylation. Either AMPK inhibition by BML-275 or SIRT1 silencing partially counteracted naringin-induced autophagic flux enhancement. These findings indicate that naringin boosts autophagic flux through SIRT1 upregulation via AMPK activation, thus protecting NP cells against inflammatory response, oxidative stress, and impaired cellular homeostasis. Naringin can be a promising inducer of restoration autophagic flux restoration for IDD.

Background. Low back pain (LBP) has the characteristics of chronic and persistence, which is a heavy social burden. Intervertebral disc degeneration (IVDD) is a major cause of LBP. The typical features of IVDD are extracellular matrix (ECM) degradation and nucleus pulposus cell (NP) apoptosis. Bushen Huoxue Formula (BSHXF) has good clinical effects on LBP. However, the mechanism of BSHXF affecting ECM and NP cells is still unclear. Aim of the Study. In this study, the impact of BSHXF on autophagy and apoptosis of NP cells was studied through the AMPK/SIRT1 pathway. Material and Methods. NP cells were extracted through the digestion of collagenase and trypsin, and the components of BSHXF were identified. Cell Counting Kit-8 was applied to detect the impact of BSHXF on NP cells. Mitochondrial function was detected using MitoTracker assay, ATP kit, and SOD kit. Autophagy and apoptosis were detected by RT-qPCR, western blotting, and flow cytometry. Results. BSHXF promoted NP cell survival in a concentration-dependent manner, and the elimination of rat serum did not increase cell proliferation; TNF-α accelerated ECM degradation, ROS accumulation, and NP cell apoptosis and decreased autophagic flux. BSHXF restored mitochondrial function and autophagic flux. In addition, AMPK/SIRT1 pathway activation was associated with IVDD. Conclusions. BSHXF regulates autophagy and enhances autophagic flux to suppress excessive ROS production and restore mitochondrial function in an AMPK/SIRT1-dependent manner. However, the protection of BSHXF on TNF-α-treated cells was eliminated by 3-MA. Furthermore, the protective impact of BSHXF on ECM degradation and apoptosis induced by TNF-α was restrained by an AMPK inhibitor. Therefore, maintaining the proper autophagy illustrates treatment strategy for IVDD.

Activation of the proinflammatory-associated cytokine, tumor necrosis factor