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

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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.