Molecular Mechanisms of Muscle Redox Signaling in Exercise and Injury

运动仍然是延长人类健康寿命的最有力的干预措施，被广泛倡导用来减缓甚至防止老年时发生的功能衰退。锻炼可以增加肌肉质量，从而防止虚弱，提高活动能力，从而提高生活质量。然而，运动增加肌肉质量的分子机制还没有被很好地理解。长期以来，氧化应激一直被视为运动的负面后果，但最近的研究结果表明，减少氧化应激可以阻止运动的有益影响，强调了运动信号在训练中的重要性。利用线粒体或胞浆中表达比率氧化还原敏感荧光蛋白(RoGFP)的转基因小鼠，我们将使用活体成像技术记录活体动物骨骼肌细胞氧化还原状态的时空动力学。我们已经发现，肌肉纤维损伤在运动过程中的氧化还原信号中起着重要作用，并伴随着肌肉纤维损伤，但尚未确定传递这一信号的途径(S)。我们将致力于确定受损肌肉纤维释放的危险相关分子模式(DAMP)以及导致邻近组织中观察到的氧化还原瞬变的受体。还将使用合适的体外模型，总体目标是获得可能有助于设计增加锻炼积极效果的干预措施的见解。在育儿假期间出版了一本书和一本书。

Exercise remains the most powerful intervention to increase health span in humans and is widely advocated to slow down or even prevent the functional decline occurring in old age. Exercise builds muscle mass, which prevents frailty, increases mobility, as a consequence, quality of life. Nevertheless, the molecular mechanisms by which exercise builds muscle mass are not well understood. Oxidative stress has long been seen as a negative consequence of exercise, but more recent results suggest that reducing oxidative stress can prevents the beneficial effects of exercise, underscoring its importance in signaling during training.Using transgenic mice expressing a ratiometric redox-sensitive fluorescent protein (roGFP) in mitochondrial or cytosol, we will record the spatio-temporal dynamics of cellular redox state in skeletal muscle of live animals using in vivo imaging. We already found that muscle fiber injury plays an important role in redox signaling during exercise and accompanying muscle fiber injury, but did not yet identify the pathway(s) transmitting this signal. We will work towards identifying the danger associated molecular patterns (DAMPs) released by injured muscle fibers and the receptors causing the observed redox transients in adjacent tissue. Suitable in vitro models will also be employed, with the overall goal of gaining insights that might help design interventions that increase the positive effects of exercise.One publication and one book chapter was published during parental leave.