Identifying Acss1, Mtfp1 and Oxct1 as key regulators and promising biomarkers of sarcopenia in various models

Mitochondrial dysfunction plays a critical role in muscular homeostasis, but the molecular mechanism underlying mitochondrial dynamics and sarcopenia awaits to be uncovered. We all know that malnutrition, cachexia, and type 2 diabetes are significant contributors to the development of sarcopenia.Therefore, we analyzed a bioinformatic analysis on cathectic differentially expressed genes (cDEGs), fasted differentially genes (fDEGs) and mitochondria-related genes. The overlapping genes identified were then validated by RT-qPCR and Western blotting experiments in various sarcopenia mice models and used to predict aging-related muscle loss in humans. First, the correlation analysis and PPI network indicated 6 overlapping candidates (Bdh1, Gdap1, Acss1, Mtfp1, Idh2, Oxct1) may constitute a regulatory effect in mitochondrial dynamics and muscle wasting. Next, we successfully established fasted, Lewis lung carcinoma (LLC) and Diabetes Mellitus (DM) induced sarcopenia mice models and verified that Acss1, Mtfp1 and Oxct1 shared common and significant variation tendency in these sarcopenia mice models. Further-more, Pearson correlation analysis showed that Acss1 was negatively related to the weight of gastrocnemius while Mtfp1 and Oxct1 displayed a significantly positive correlation with gastrocnemius weight in sarcopenic mice model induced by LLC, fasting and DM. What's more, ROC analysis based on human aging-related datasets indicated Acss1, Mtfp1, Oxct1 had outstanding diagnostic capabilities for sarcopenia. In general, we identified three hub genes (Acss1, Mtfp1 and Oxct1) that are strongly associated with mitochondrial dysfunction in sarcopenia and may provide novel and reliable indicators for screening, diagnosis, and prognosis, as well as potential therapeutic targets for patients with sarcopenia.