Molecular Mechanisms of Muscle Redox Signaling in Exercise and Injury

运动仍然是增加人类健康寿命的最有力的干预措施，并被广泛提倡减缓甚至预防老年人的功能衰退。运动建立肌肉质量，防止脆弱，增加流动性，因此，生活质量.然而，运动建立肌肉质量的分子机制还没有很好的理解。长期以来，氧化应激一直被认为是运动的负面后果，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效果，强调其在训练过程中的信号传导的重要性。使用转基因小鼠在线粒体或细胞质中表达比例氧化还原敏感荧光蛋白（roGFP），我们将使用活体成像记录活体动物骨骼肌中细胞氧化还原状态的时空动力学。我们已经发现，肌纤维损伤在运动和伴随的肌纤维损伤期间的氧化还原信号中起着重要作用，但尚未确定传递此信号的途径。我们将致力于确定由受损肌肉纤维释放的危险相关分子模式（DAMP）和引起邻近组织中观察到的氧化还原瞬变的受体。还将采用合适的体外模型，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份出版物和一本书的一个章节。

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.