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Calorie restriction (CR) extends daily life span and therefore ameliorates age-related pathologies in most species studied, nevertheless the mechanisms underlying these Hedgehog results continue to be unclear. Applying mouse skeletal muscle as a model, we demonstrate that CR acts in component by improving the perform of tissue-specific stem cells. Even short-term CR significantly enhanced stem cell availability and exercise during the muscle of young and outdated animals, in concert with a rise in mitochondrial abundance and induction of conserved metabolic and longevity regulators. Moreover, CR enhanced endogenous muscle restore and CR initiated in both donor or recipient animals improved the contribution of donor cells to regenerating muscle immediately after transplant. These research indicate that metabolic factors play a vital role in regulating stem cell perform and that this regulation can influence the efficacy of recovery from damage plus the engraftment of transplanted cells.