Cellular energy demands are readily changed during physical exercise resulting in adaptive responses by signaling proteins of metabolic processes, including the NAD+ dependent lysine deacetylase SIRT1. Regular exercise results in systemic adaptation that restores the level of SIRT1 in the kidney, liver, and brain in patients with neurodegenerative diseases, and thereby normalizes cellular metabolic processes to attenuate the severity of these diseases. In skeletal muscle, over-expression of SIRT1 results in enhanced numbers of myonuclei improves the repair process after injury and is actively involved in muscle hypertrophy by up-regulating anabolic and downregulating catabolic processes. The present review discusses the different views of SIRT1 dependent deacetylation of PGC-α.
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