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BACKGROUND: Studies have shown that short-chain fatty acids (SCFAs) are a potential regulator of skeletal muscle energy metabolism, but the exact mechanism is unclear. OBJECTIVE: To observe the effect of SCFAs on aged rats with sarcopenia and to explore the underlying mechanism. METHODS: Sprague-Dawley rats were randomly divided into control group, sarcopenia group, and sarcopenia + SCFAs group (SCFAs group). In the latter two groups, rat models of sarcopenia were established using ovariectomized rats injected with 5 mg/kg dexamethasone for 7 days. In the control group, the abdominal cavity was only exposed but not removed, and then sutured. Rats in the SCFAs group were administered drinking water containing 150 mmol/L short-chain fatty acids, 600 mg/kg sodium acetate, 200 mg/kg sodium propionate, and 200 mg/kg sodium butyrate for 4 weeks. Rats in the control and sarcopenia groups were given the same volume of normal saline. Successful modeling was assessed by measuring the bilateral gastrocnemius muscle mass and body mass to calculate the gastrocnemius index after modeling. Food intake, body mass and grip strength of rats were measured at 0, 1, 2 and 4 weeks after successful modeling; morphological changes of gastrocnemius muscle were observed by hematoxylin-eosin staining; and the expression of p-AMPK and p-ULK1 proteins in gastrocnemius muscle was detected by western blot. RESULTS AND CONCLUSION: Compared with the control group, the sarcopenia group showed significantly decreased body mass, food intake, forelimb grip strength (P < 0.05), wet mass of gastrocnemius muscle (P < 0.05), and protein levels of p-AMPK and p-ULK1 (P < 0.05). Compared with the sarcopenia group, the SCFAs group showed a significant increase in food intake, body mass, grip strength, wet mass of gastrocnemius muscle, and protein levels of p-AMPK and p-ULK1 in gastrocnemius muscle (P < 0.05). All these findings indicate that SCFAs improve symptoms of sarcopenia in the elderly and may be associated with the upregulation of AMPK and ULK1 proteins in skeletal muscle. [ABSTRACT FROM AUTHOR]

Objective Based on the Gene Expression Omnibus （GEO） database, our aim is to identify potential mitophagy-related genes for sarcopenia and to observe their expression changes in skeletal muscle tissues of patients with sarcopenia. Methods Gene expression datasets for sarcopenia （GSE1428） were obtained from the GEO database and differentially expressed genes （DEGs） in the sarcopenia samples and normal samples were screened. The DEGs of sarcopenia were intersected with mitophagy-related genes using the "VennDiagram" package to obtain mitophagy-related DEGs of sarcopenia. The biological functions of mitophagy-related DEGs for sarcopenia were analyzed using Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG). The mitophagy-related target genes for sarcopenia were selected using Cytoscape, and the expression changes of these genes in skeletal muscle tissues of patients with sarcopenia and controls were observed in the gene expression datasets GSE136344 for sarcopenia. Results Ninety-nine mitophagy-DEGs for sarcopenia were screened out. As shown by KEGG enrichment analyses, these genes were significantly enriched in pathways responsible for neurodegeneration-multiple diseases, Parkinson's disease, prion disease, and so on. GO function annotation showed that DEGs were mostly located in the mitochondrial inner membrane and mitochondrial protein-containing complex, where they were engaged in biological processes such as energy metabolism, cellular respiration, and oxidative phosphorylation. They were also involved in the molecular functions of active transmembrane transporter activity, etc. The inner membrane mitochondrial protein （IMMT), dynamin 1-like （DNM1L), and ATP5A1 were identified as the mitophagy-related target genes for sarcopenia. Sarcopenic patients exhibited lower expression levels of IMMT and DNM1L in their skeletal muscles in comparison with non-sarcopenic individuals （all P<0. 05). Conclusions IMMT and DNM1L were identified as significant mitophagy-related target genes for sarcopenia. These target genes contributed to the pathogenesis of Sarcopenia not on‐ ly by affecting neurodegeneration-multiple diseases pathways, Parkinson's disease pathway, and prion disease pathway but also by participating in biological processes such as energy metabolism, cellular respiration, and oxidative phosphorylation. Patients with sarcopenia exhibited lower expression levels of IMMT and DNM1L in skeletal muscle tissues. [ABSTRACT FROM AUTHOR]