Identification of the shared gene signatures and pathways between sarcopenia and type 2 diabetes mellitus.

Abstract

Sarcopenia is characterized by the age-associated loss of skeletal muscle mass and strength that develops progressively and plays an important role in the disability of the elderly. It has received growing attention over the last decade and has been implicated as both a cause and consequence of type 2 diabetes mellitus (T2DM). The existence of T2DM could increase the risk of developing sarcopenia through multiple mechanisms including advanced glycation end-product accumulation. Meanwhile, sarcopenia would alter glucose disposal and may contribute to the development and progression of T2DM due to reduced muscle mass. We implemented transcriptomic analysis of skeletal muscle biopsy specimens in sarcopenia patients and proliferating myoblasts or differentiated myotubes from individuals with T2DM. Related microarray data were selected from Gene Expression Omnibus (GEO) to screen the genes, which were differentially expressed for sarcopenia and T2DM. Multiple combinatorial statistical methods and bioinformatics tools were used to analyze the common DEGs. Meanwhile, functional enrichment analysis was also carried out. Furthermore, we constructed the protein-protein interaction (PPI), as well as transcription factor (TF)-gene interactions network and TF-miRNA coregulatory network. Finally, based on the common DEGs, drug compounds were speculated using the Drug Signatures database (DSigDB). A total of 1765 and 2155 DEGs of sarcopenia and T2DM were screened, respectively. 15 common genes (LXN, CIB2, PEA15, KANK2, FGD1, NMRK1, PLCB1, SEMA4G, ADARB1, UPF3A, CSTB, COL3A1, CD99, ETV3, FJX1) correlated with sarcopenia and T2DM simultaneously were then identified, and 3 genes (UPF3A, CSTB and PEA15) of them were regarded as hub genes. Functional enrichment analysis revealed several shared pathways between two diseases. In addition, according to the TF-gene interactions network and TF-miRNA coregulatory network, part of TF and miRNA may be identified as key regulator in sarcopenia and T2DM at the same time (e.g., CREM and miR-155). Notably, drug compounds for T2DM and sarcopenia were also suggested, such as coenzyme Q10. This study revealed that sarcopenia and T2DM may share similar pathogenesis and provided new biological targets and ideas for early diagnosis and effective treatment of sarcopenia and T2DM.