Integrated transcriptomic analysis identifies lysosomal autophagy-related genes in sarcopenia

Area of Science:

• Gerontology and Molecular Biology: Investigating the molecular underpinnings of age-related muscle loss.

Background:

• Sarcopenia (SARC) significantly impacts elderly quality of life and healthcare costs.
• Current SARC treatments have limited efficacy and variable patient responses.

Purpose of the Study:

• To identify novel therapeutic targets for SARC by analyzing lysosomal autophagy-related differentially expressed genes (LARDEGs).
• To explore the molecular pathways and immune microenvironment associated with SARC.

Main Methods:

• Analysis of Gene Expression Omnibus microarray datasets (GSE8479, GSE1428) to identify SARC-related differentially expressed genes (DEGs).
• Utilized Gene Ontology, KEGG pathway analysis, PPI network analysis, and GSEA to assess biological functions and pathways.
• Examined immune cell infiltration in SARC samples.

Main Results:

• Identified 12 key LARDEGs (e.g., BHLHE41, CDKN1A, RPS27A) correlated with energy metabolism and mitochondrial function.
• Constructed a protein-protein interaction network revealing six crucial hub genes (e.g., BHLHE41, UBE2D1, CDKN1A) as potential therapeutic targets.
• Found significant differences in resting NK cells and M2 macrophages, with CDKN1A correlating with M2 macrophages and inversely with NK cells.

Conclusions:

• The identified LARDEGs and hub genes provide novel insights into SARC pathogenesis.
• The immune microenvironment plays a critical role in SARC, suggesting potential for immunotherapeutic strategies.
• Further validation is required for clinical translation of these findings.