Novel fatigue-related mechanisms driving post-exercise recovery and skeletal muscle adaptations and dysfunction

众所周知，运动是导致骨骼肌重构的最重要的刺激因素之一。当肌肉在剧烈运动中变得疲惫时，这些运动诱导的适应被最大程度地激活。然而，根据所进行的运动类型的不同，疲劳可以导致不同的骨骼肌适应，包括增加肌肉耐力或增加肌肉力量和质量。目前，疲劳触发这些不同的生理适应的确切机制还不是很清楚。一个可能与这些适应性反应相关的有效信号分子是肌内胞浆钙。疲劳性运动如何以及为什么调节胞浆钙流量仍不清楚。本计划旨在通过1)了解疲劳导致耐力训练适应的机制(S)，2)确定疲劳导致抵抗力训练适应的机制(S)，以及3)评估目标1和2在人类自然适应状态下如何潜在地改变，来解决钙的作用。目前关于疲劳对运动的影响的知识主要是描述性的，很少有研究试图通过改变肌肉疲劳的程度来确定骨骼肌适应的早期标志。我们的研究可能会为理解疲劳如何调节骨骼肌中运动诱导的训练适应提供一个“缺失的环节”。这项工作将为未来实施疲劳运动以优化人类健康和身体福祉的战略提供基础。

Exercise is known to be one of the most important stimuli that causes skeletal muscle remodeling. These exercise-induced adaptations are activated to the greatest extent when muscle becomes fatigued during strenuous exercise. However, depending on the type of exercise performed, fatigue can result in diverse skeletal muscle adaptations, including increased muscle endurance or increased muscle strength and mass. At present, the exact mechanisms by which fatigue may trigger these distinct physiological adaptations is not well-understood. One potent signaling molecule potentially linked to these adaptive responses is intramuscular cytosolic calcium. How and why fatiguing exercise modulates the cytosolic calcium flux remains unclear. This program aims to address the role of calcium by 1) understanding the mechanism(s) through which fatigue results in endurance training adaptations, 2) identifying the mechanism(s) by which fatigue results in resistance training adaptations, and 3) to assess how aims 1 and 2 are potentially altered in the naturally adapted state of human aging. The current knowledge regarding the effects of fatigue on exercise is largely descriptive and few studies have attempted to modify the extent of muscle fatigue to identify the early markers of skeletal muscle adaptation. Our studies may provide a "missing link" for understanding how fatigue regulates exercise-induced training adaptations in skeletal muscle. This work will provide a foundation for future strategies toward implementing fatiguing exercise in optimizing the health and physical wellbeing of humans.