Identification of Mitochondria- and Macrophage Activation-Related Hub Genes in Sarcopenia.

Abstract

To explore the hub genes and pathways associated with sarcopenia progression from the perspective of mitochondrial dysfunction and macrophage activation. The GEO datasets GSE8479, GSE1428 and GSE136344 were obtained from the GEO database. Mitochondria-related genes (MRGs) and macrophage activation-related genes (MARGs) were identified. Functional enrichment analyses, PPI analysis, diagnostic model construction, molecular subtyping and ssGSEA-based immune enrichment analysis were performed. Key genes were further validated by RT-qPCR. A total of 62 mitochondria- and macrophage activation-related differentially expressed genes (M&MARDEGs) were identified. Nine key genes (IGF1, FTL, MAPK8, MAPK9, TF, CREB1, FAS, VEGFA and NFKB1) were retained in the final diagnostic model. Immune enrichment analysis suggested distinct immune-related transcriptional characteristics among different risk groups and molecular subtypes. RT-qPCR validation demonstrated that IGF1, FAS and MAPK9 were significantly downregulated, whereas FTL, TF, CREB1 and NFKB1 were significantly upregulated in the sarcopenia model group. MAPK8 and VEGFA showed decreasing trends without statistical significance. Integrated transcriptomic analysis identified key genes potentially associated with sarcopenia through the intersection of mitochondrial dysfunction and macrophage activation. These findings provide insights into the molecular characteristics of sarcopenia and may offer candidate targets for future mechanistic and translational studies.