Molecular and Cellular Exercise Physiology, Department of Physiology and Pharmacology, Biomedicum. Karolinska Institute, Stockholm, Sweden.
Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States.
Front Endocrinol (Lausanne). 2020 Oct 26;11:591476. doi: 10.3389/fendo.2020.591476. eCollection 2020.
Increasing exercise capacity promotes healthy aging and is strongly associated with lower mortality rates. In this study, we analyzed skeletal muscle transcriptomics coupled to exercise performance in humans and rats to dissect the inherent and response components of aerobic exercise capacity. Using rat models selected for intrinsic and acquired aerobic capacity, we determined that the high aerobic capacity muscle transcriptome is associated with pathways for tissue oxygenation and vascularization. Conversely, the low capacity muscle transcriptome indicated immune response and metabolic dysfunction. Low response to training was associated with an inflammatory signature and revealed a potential link to circadian rhythm. Next, we applied bioinformatics tools to predict potential secreted factors (myokines). The predicted secretome profile for exercise capacity highlighted circulatory factors involved in lipid metabolism and the exercise response secretome was associated with extracellular matrix remodelling. Lastly, we utilized human muscle mitochondrial respiration and transcriptomics data to explore molecular mediators of exercise capacity and response across species. Human transcriptome comparison highlighted epigenetic mechanisms linked to exercise capacity and the damage repair for response. Overall, our findings from this cross-species transcriptome analysis of exercise capacity and response establish a foundation for future studies on the mechanisms that link exercise and health.
增加运动量可以促进健康老龄化，并且与降低死亡率密切相关。在这项研究中，我们分析了人类和大鼠的骨骼肌转录组学与运动表现的关系，以剖析有氧运动能力的固有和响应成分。使用因内在和获得性有氧能力而选择的大鼠模型，我们确定高有氧能力肌肉的转录组与组织氧合和血管生成的途径有关。相反，低能力肌肉的转录组表明存在免疫反应和代谢功能障碍。对训练的低反应与炎症特征相关，并揭示了与昼夜节律的潜在联系。接下来，我们应用生物信息学工具来预测潜在的分泌因子（肌因子）。预测的运动能力的分泌组特征突出了涉及脂质代谢的循环因子，而运动反应的分泌组与细胞外基质重塑有关。最后，我们利用人类肌肉线粒体呼吸和转录组学数据来探索跨物种运动能力和反应的分子介质。人类转录组比较突出了与运动能力相关的表观遗传机制，以及对反应的损伤修复。总的来说，我们对运动能力和反应的跨物种转录组分析的发现为研究运动与健康之间的联系机制奠定了基础。
