Objective To explore the potential regulatory mechanism of resistance exercise in senescence accelerated-prone 8 mice(SAMP8)by evaluating the effects of exercise on the expression of long non-coding RNA(lncRNA)and mRNA in quadriceps muscles by RNA-sequencing(RNA-seq)technology.Methods Twenty-eight-week-old male SAMP8 mice were divided into a model group(M group)and resistance-exercise group(R group)(n=6 mice per group).Another eight normally aging SAMR1 mice of the same age were used as the control group(C group).Mice in R group received 8 weeks of increasing weight climbing exercise training.Relative grip strength was measured every week and the rotarod test was performed every 2 weeks.Histological changes in the right quadriceps femoris were observed by hematoxylin-eosin staining and the left quadriceps was used for RNA-seq.Differentially expressed lncRNA and mRNA were screened and analyzed for enrichment by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses.Finally,key differentially expressed genes were analyzed by quantitative reverse transcription-polymerase chain reaction to verify the accuracy of the RNA-seq result.Results(1)Relative grip strength and rotarod test time were significantly decreased in M group compared with C group(P＜0.01),but were significantly increased after 8 weeks of Rgroup compared with M group(P＜0.01).(2)The cross-sectional area of the muscle fibers was significantly lower in M group compared with C group,as shown by HE staining(P＜0.01),while the cross-sectional area of the muscle fibers was significantly increased in the R group compared with M group(P＜0.01).(3)Differential expression analysis identified 182 upregulated and 218 downregulated lncRNA,and 454 upregulated and 289 downregulated mRNA between M group and R group.The KEGG pathways of lncRNA target genes that were differentially expressed between M group and R group were significantly enriched in intestinal immune network for IgA production,nuclear factor-kappa B signaling pathway,and inflammatory bowel disease.Conclusions(1)This study demonstrated that resistance exercise can improve skeletal muscle function in SAMP8 mice with sarcopenia.We identified lncRNA and mRNA that were differentially expressed as a result of resistance exercise,and which might be potential targets of sarcopenia therapy.(2)Furthermore,analyzing the biological functions of the target genes of the differentially expressed lncRNA and mRNA may further our understanding of the mechanism of resistance exercise for improving sarcopenia.

Objective:To explore the mechanism of resistance exercise improving sarcopenia through JAK2/STAT5a path-way based on transcriptomics.Method:Sixteen 28-week-old male SAMP8 mice were randomly divided into an aging model group(Group M)and a resistance training group(Group R);another eight age-matched male anti-aging mice(SAMR l)were set up as Group C(the young control group).Groups C and Group M were routinely housed without any interventions,and Group R underwent 8 weeks of incremental load ladder climbing training.The relative grip strength and rotating rod time were measured every two weeks,and at the end of the intervention,the relative muscle mass of the mice was tested and the cross-sectional area of muscle fibers was observed;RNA-seq technology was used to build libraries for transcriptome sequencing,to screen for differentially expressed genes,and to enrich relevant physiological characteristics and highly relevant signaling pathways through GO,KEGG enrichment,with PPI screening for related core genes;RT-qPCR was used to detect mRNA expression of IL-6,Jak2,Stat5a and Socs3 in skeletal muscle.Result:①Relative grip strength,rotating rod time and muscle mass of the mice showed that group M was significantly lower than group C(P＜0.001),while group R was significantly higher than group M(P＜0.05);The HE staining of muscle cross-sectional area showed group M was significantly lower than group C(P＜0.001),while group R was significantly higher than group M(P＜0.05);Transcriptomic differential gene screening:a total of 572 DEGs were screened between groups R and M,with 231 mRNA expressions upregu-lated and 341 mRNA expressions downregulated in group R compared to group M(FC≥0,P＜0.05);JAK-STAT signaling pathway was found to be highly expressed by enrichment analysis of DEGs GO and KEGG;PPI screened for the core genes of sarcopenia core genes JAK2,STAT5a.RT-qPCR results showed that com-pared to group C,the gene expression levels of IL-6,Jak2,and STAT5a in skeletal muscle in group M were significantly increased(P＜0.01),and the expression level of Socs3 was significantly decreased(P＜0.01);com-pared with group M,the levels of IL-6 mRNA,JAK2,and STAT5a in skeletal muscle in group R were sig-nificantly decreased(P＜0.05),while the levels of Socs3 were significantly elevated(P＜0.01).Conclusion:Resistance exercise can improve sarcopenia in SAMP8 mice by inhibiting the JAK2/STAT5a pathway.

Objective:To explore the mechanism of resistance exercise improving sarcopenia through JAK2/STAT5a path-way based on transcriptomics.Method:Sixteen 28-week-old male SAMP8 mice were randomly divided into an aging model group(Group M)and a resistance training group(Group R);another eight age-matched male anti-aging mice(SAMR l)were set up as Group C(the young control group).Groups C and Group M were routinely housed without any interventions,and Group R underwent 8 weeks of incremental load ladder climbing training.The relative grip strength and rotating rod time were measured every two weeks,and at the end of the intervention,the relative muscle mass of the mice was tested and the cross-sectional area of muscle fibers was observed;RNA-seq technology was used to build libraries for transcriptome sequencing,to screen for differentially expressed genes,and to enrich relevant physiological characteristics and highly relevant signaling pathways through GO,KEGG enrichment,with PPI screening for related core genes;RT-qPCR was used to detect mRNA expression of IL-6,Jak2,Stat5a and Socs3 in skeletal muscle.Result:①Relative grip strength,rotating rod time and muscle mass of the mice showed that group M was significantly lower than group C(P＜0.001),while group R was significantly higher than group M(P＜0.05);The HE staining of muscle cross-sectional area showed group M was significantly lower than group C(P＜0.001),while group R was significantly higher than group M(P＜0.05);Transcriptomic differential gene screening:a total of 572 DEGs were screened between groups R and M,with 231 mRNA expressions upregu-lated and 341 mRNA expressions downregulated in group R compared to group M(FC≥0,P＜0.05);JAK-STAT signaling pathway was found to be highly expressed by enrichment analysis of DEGs GO and KEGG;PPI screened for the core genes of sarcopenia core genes JAK2,STAT5a.RT-qPCR results showed that com-pared to group C,the gene expression levels of IL-6,Jak2,and STAT5a in skeletal muscle in group M were significantly increased(P＜0.01),and the expression level of Socs3 was significantly decreased(P＜0.01);com-pared with group M,the levels of IL-6 mRNA,JAK2,and STAT5a in skeletal muscle in group R were sig-nificantly decreased(P＜0.05),while the levels of Socs3 were significantly elevated(P＜0.01).Conclusion:Resistance exercise can improve sarcopenia in SAMP8 mice by inhibiting the JAK2/STAT5a pathway.