In 1989, Rosenberg emphasized the importance of the loss of skeletal muscle mass that occurs with aging and coined the term ‘sarcopenia’. Since then, sarcopenia has attracted considerable attention due to the aging population. This muscle loss is associated with increased risk of adverse health outcomes, including falls, morbidity, loss of independence, disability, and mortality. Thus, it is necessary to screen the key genes and pathways related to the progression of sarcopenia. In the present study, we integrated gene expression profiles of 12 sarcopenia samples and 10 normal samples from a GEO dataset (GSE1428) and analyzed the data using bioinformatics tools. A total of 603 DEGs with |log2 FC| ≥ 0.5 in sarcopenia compared with normal samples were selected. Furthermore, 10 potential crucial genes (CD4,PLK1,CHEK2,LCP2,NANOG,PTPN11,RUNX2,ANXA5,BUB1B,CCR5), and several important pathways, which were associated with sarcopenia risk, were identified, suggesting these may play important role in the mechanism of sarcopenia.
T lymphocytes are essential for skeletal muscle regeneration and repair. Lymphocytes and their secreted proteins play a crucial role in muscle repair and regeneration, considered as a potential control switch for this process. T Lymphocytes can also affect the proliferation and migration of muscle satellite cells, which may be associated with reduced muscle mass in patients with sarcopenia. CD4 can regulate the sensitivity and output of T cell responses and most critically contribute to the T cell function in vivo and thus are known as coreceptors of T-cell receptors(TCR).It also contribute to T-cell development, homeostasis and antigenic response. It has extremely low affinity for its ligand but which is also essential in T-cell development and in the removal of pathogens during T cell-dependent immune responses. Bharath et al indicated that aging compromises autophagy in CD4 + T lymphocytes to stimulate the secretion of several pro-inflammatory interleukins, thus contributing to inflammaging. Lymphocyte cytosolic protein 2 (LCP2) is one of the SLP‑76 family of adapters, which are critical intermediates in signal cascades downstream of several receptors. LCP2 regulates immunoreceptor signaling (such as T‑cell receptors) and it is also required for integrin signaling in neutrophils and platelets. It plays an important role in NK-cell mediated recognition of missing-self targets10 and positively regulates antigen-induced mast cell activation by recruiting BCR. Quantitative reductions of LCP2 trigger immune dysregulation with the excessive production of proinflammatory cytokines and autoantibodies. These studies indicate that LCP2 deeply participates in immune responses through the regulation of immune cells. We found that CD4 and LCP2 were enriched in KEGG term of T cell receptor signaling pathway. These results indicated that CD4 and LCP2 might be the potential biomarkers of sarcopenia.
In our study,CD4 and C-C motif chemokine receptor 5(CCR5 )were enriched in KEGG term of Cytokine-cytokine receptor interaction and Human immunodeficiency virus 1 infection.CCR5 and its ligands may play a role in various inflammatory diseases, as cellular activation of CCR5 normally happens through chemokine binding, which then regulate intracellular trafficking and protective cellular and humoral responses. Indeed, the migration of lymphocytes to inflammatory areas is controlled by chemokine gradients. CCR5 is expressed in inflammatory cells infiltrating the central nervous system in vivo. It is also expressed on immune cells within inflammatory lesions in multiple sclerosis(MS) and may contribute to recruitment of these cells to the inflamed tissue or to their activation.
Polo-like kinase 1 (PLK1) is a conserved mitotic serine-threonine protein kinase, functions as a regulatory protein, and is involved in the progression of the mitotic cycle. It plays important roles in the regulation of cell division, maintenance of genome stability, in spindle assembly,mitosis, and DNA-damage response. A role for PLK1 has been recently described in diverse immune disorders including Graft versus Host Disease, where it contributes to immunological responses of alloreactive T cells. Also, in neurological disorders such as Huntington’s disease and Alzheimer’s disease, activity of PLK1 is altered in affected neurons. checkpoint kinase 2(CHEK2 )kinase was reported to be involved in the processes of DNA damage repair (DDR) and cell cycle regulation.It also has been linked to cell protection via autophagy in response to oxidative stress.High levels of reactive oxygen species (ROS) and hypoxia were reported to trigger the ATM-CHK2 axis and the phosphorylation of Beclin 1. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a conserved multifunctional protein that is vital for the function of mitotic spindle checkpoint and correcting kinetochore-microtubule attachments. Our study revealed that the PLK1、CHEK2、BUB1B expression level was down-regulated in sarcopenia samples compared to normal samples. Enrichment analyses in the present study indicated that PLK1、CHEK2and BUB1B were enriched in KEGG term of cell cycle. Yin J et al. indicated that the differentiation of satellite cells is a fundamental process for the maintenance of muscle trophism. The multi-signal pathway cascade regulates the cell cycle process, and plays a crucial role in promoting myoblasts growth. Thus, downregulation of PLK1, CHEK2and BUB1B may inhibit the growth of satellite cells, leading to sarcopenia.
Nanog homeobox(NANOG) is a stem cell transcription factor that plays a major role in regulation of human development. It is involved in cell fate determination, proliferation, and apoptosis. Notably, ectopic expression of NANOG preserved the morphology and restored the myogenic differentiation capacity of late passage myoblasts, possibly by restoring the expression level of myogenic factors.So, NANOG might be the a potential biomarker of sarcopenia.
It have also confirmed that testosterone can promote the number of stellate cells in a dose-dependent manner and is the main regulator of their function in vitro.Moreover, testosterone levels in men decrease by about 1% a year with age, which plays an important role in the development of sarcopenia.ANXA5, also known as Annexin A5, is a member of the annexin family of proteins,which can bind to calcium and phospholipid, acting as an endogenous regulator of various physiological processes .Moreover, Yao et al. found ANXA5 was highly expressed in rat Leydig and Sertoli cells and could involve in the regulation of testosterone synthesis and secretion. Gidrol et al. found that ANXA5 might exert antioxidant function in some cases. Ewing et al. found that ANXA5 been believed closely related to inflammatory response and cell apoptosis[48, 49].Similarly, Protein tyrosine phosphatase non-receptor type 11(PTPN11) mutations induce metabolic changes that increase the ability of mutated cells to utilize multiple energy sources. It is involved in numerous signal transduction functions important for normal hematopoiesis, including proliferation,differentiation, and apoptosis. In Leydig cells, PTPN11 supports mitochondrial fusion and the expression of acyl-CoA synthetase (ACSL4) needed for the production of steroids including testosterone.
Bones also affect muscles through mechanical and chemical processes. Osteoblasts or factors secreted by osteocytes, such as osteocalcin, osteostin and fibroblast growth factor − 23, may regulate muscle. Osteocalcin may also affect glucose, lipid and energy metabolism, thereby affecting muscle function.Runt-related transcription factor 2 (RUNX2) was first described as an essential regulator of skeletal development. Post-translational regulation modulates the activity, stability and function of many proteins including transcription factors. Phosphorylation, acetylation, and ubiquitination are the most representative post-translational modifications and also phosphorylation-directed conformational changes by enzymes play key roles in regulating protein activity. 
In current study, we have discussed that 10 potential crucial genes are involved in the currence and development of sarcopenia, suggesting these genes may serve as potential biomarkers and therapeutic targets for sarcopenia. However, the limitations of this study should be considered. First of all, this is a retrospective study that requires external verification to verify our findings; Secondly, the function of the hub gene needs to be further verified in an in vitro model, which will be the focus of our future work.