Calorie restriction extends life span in organisms ranging from yeast to mammals. Nisoli et al. find that when mice are subjected to calorie restriction, endothelial nitric oxide synthase (eNOS) expression and 3′,5′-cyclic guanosine monophosphate formation are increased. This change is accompanied by mitochondrial biogenesis, increased oxygen consumption, adenosine triphosphate production, and expression of sirtuin 1, a protein previously implicated in mediating the effects of calorie restriction on life span. These effects are strongly attenuated in mutant mice lacking eNOS. Thus, NO may play a role in the processes induced by calorie restriction and in life-span expansion in mammals.
E. Nisoli, C. Tonello, A. Cardile, V. Cozzi, R. Bracale, L. Tedesco, S. Falcone, A. Valerio, O. Cantoni, E. Clementi, S. Moncada, M. O. Carruba, Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310, 314-317 (2005). [Abstract] [Full Text]