Abstract: Objective To explore the changes of miRNA and mRNA during muscle aging through integrating high-throughput microRNA(miRNA)/mRNA expression data. Methods Two different age(6 and 24 months) mice gastrocnemius miRNA databases were used, and the combined analysis of “differential miRNA targeted regulatory genes” and differential mRNA was carried out. The core regulatory network in the skeletal muscle aging process was constructed. GSEA software was used to analyze the gene ontology(GO) function and Kyoto encyclopedia of genes and genomes(KEGG )signaling pathway involved in the differential gene. Representative differential miRNA and targeted mRNA expression were detected by real-time fluorescent quantitative PCR (qRT-PCR)and Western blot. Results A total of 877 and 84 differentially expressed genes and miRNAs were identified in the skeletal muscle of young and old mice, respectively. The construction of a miRNA-mRNA network resulted in 21 miRNAs, and among them, there were 9 miRNAs with more than 7 target genes, and the qRT-PCR verification is consistent with the sequencing results. Pathway analysis showed that the differential genes were mainly related to transcription, metabolism and skeletal muscle differentiation. The skeletal muscle differentiation process contained early growth response protein 2(EGR2), Ring1, transcription factor Yin-Yang1(YY1)and Ring1 andYY1-binding protein(Rybp). qRT-PCR verified that the mRNA levels of 4 genes increased during skeletal muscle differentiation. Rybp also increased in protein levels. Conclusions miRNA may promote muscle aging through interventing the processes such as transcription, metabolism and skeletal muscle differentiation. Rybp and its presumed regulatory miRNA miR-136 may promote the aging process of muscles.

Key words: muscle aging, miRNA, genes, skeletal muscle