Comprehensive transcriptomic profiling reveals lncRNA-miRNA-mRNA regulatory networks in skeletal muscle aging of mice

PURPOSE: As organisms age, physiological and pathological changes occur, with altered lncRNA expression playing a key role. However, their regulatory mechanisms in aging remain unclear. This study investigates the differential expression of lncRNAs between aged and young mice, and explores the lncRNA-miRNA-mRNA interplay to gain insights into the molecular basis of aging. METHODS: We performed whole-transcriptome sequencing on tibialis anterior muscles from four aged (20-month-old) and four young (3-month-old) mice. Hub genes were identified via PPI and WGCNA analyses, followed by functional enrichment. Integrative analysis revealed interactions among differentially expressed lncRNAs, miRNAs, and mRNAs, leading to the construction of cis-/trans-regulatory and ceRNA networks. RESULTS: Our results revealed 746 significantly differentially expressed known lncRNAs (465 upregulated, 281 downregulated) and 27 novel lncRNAs in aged mouse TA muscle, alongside 50 miRNAs and 1124 mRNAs. Based on lncRNA classification (antisense, intergenic, intronic), we constructed subtype-specific cis- and trans-regulatory networks. Hub genes were identified via PPI and WGCNA analyses to further refine these networks. Highly expressed and variable genes were also integrated into regulatory mapping. Enrichment analyses indicated involvement in extracellular matrix remodeling, epithelial cell migration, and immune response. CONCLUSIONS: This study systematically profiled age-related changes in lncRNAs, miRNAs, and mRNAs in TA muscle, and constructed core regulatory networks based on lncRNA subtypes. This study systematically profiled age-related transcriptomic changes in mouse skeletal muscle and constructed lncRNA-miRNA-mRNA regulatory networks associated with aging. These results provide a valuable resource and generate hypotheses for future experimental validation of lncRNA-mediated regulatory mechanisms in muscle aging.