Identification of biomarkers associated with glycolysis and lactation in sarcopenia

Sarcopenia, characterized by the loss of muscle mass, is a primary contributor to frailty among the elderly population. In recent years, several studies have highlighted the relationship between sarcopenia and glycolysis as well as lactylation; however, the underlying mechanisms remain unclear. This study aims to investigate the mechanisms linking sarcopenia with glycolysis and lactylation through bioinformatics approaches, thereby providing insights for potential therapeutic strategies in managing related diseases. We obtained the sarcopenia dataset from the Gene Expression Omnibus (GEO) database, The data sets were performed differential analysis and weighted correlation network analysis (WGCNA) analysis. Glycolysis and lactylation-related genes were obtained using MSigDB database, and intersection with disease genes was performed to obtain hub genes. Additionally, CIBERSORT was employed to analyze immune cell infiltration of common genes, while single-cell RNA sequencing data was utilized to examine the expression distribution and intercellular communications of hub genes. Finally, we predicted the upstream miRNA of the MDH1 gene using the miRBase database and constructed a relationship network between miRNAs and hub genes utilizing Cytoscape software. Subsequently, we acquired a miRNA dataset related to sarcopenia from the GEO database for differential analysis in order to validate the upstream miRNA of the MDH1 gene. By conducting differential analysis, WGCNA analysis, and Venny screening analysis, we identified a hub gene: MDH1, which is involved in glycolysis and lactylation. Further investigation into the correlation between hub genes and immune cell infiltration revealed that MDH1 exhibited the most significant association with regulatory T cells (Tregs). Results from single-cell analysis indicated that the expression of the MDH1 gene was predominantly high in myonuclei and NKT cells. Through a search of the miRBase database, we predicted 29 upstream microRNAs associated with the MDH1 gene. Following differential analysis of the miRNA dataset, we ultimately identified hsa-miR-1263 as the upstream microRNA for MDH1. In this study, we propose that hsa-miR-1263 plays a regulatory role in the onset and progression of sarcopenia by mediating glycolysis and lactylation pathways, primarily through the MDH1 gene in myonuclei and NKT cells. This research introduces for the first time the relationship between the hsa-miR-1263/MDH1 axis and sarcopenia, offering new insights into the mechanisms underlying glycolysis and lactylation in sarcopenia.