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Science 14 October 2005:
Vol. 310. no. 5746, pp. 314 - 317
DOI: 10.1126/science.1117728
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Reports

Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS

Enzo Nisoli,1,2* Cristina Tonello,1 Annalisa Cardile,1 Valeria Cozzi,1 Renata Bracale,1 Laura Tedesco,1 Sestina Falcone,1,3 Alessandra Valerio,1 Orazio Cantoni,4 Emilio Clementi,1,3,5 Salvador Moncada,6 Michele O. Carruba1,2

Calorie restriction extends life span in organisms ranging from yeast to mammals. Here, we report that calorie restriction for either 3 or 12 months induced endothelial nitric oxide synthase (eNOS) expression and 3',5'-cyclic guanosine monophosphate formation in various tissues of male mice. This was accompanied by mitochondrial biogenesis, with increased oxygen consumption and adenosine triphosphate production, and an enhanced expression of sirtuin 1. These effects were strongly attenuated in eNOS null-mutant mice. Thus, nitric oxide plays a fundamental role in the processes induced by calorie restriction and may be involved in the extension of life span in mammals.

1 Integrated Laboratories Network, Department of Preclinical Sciences, Luigi Sacco Hospital, Milan University, 20157 Milan, Italy.
2 Istituto Auxologico Italiano, 20149 Milan, Italy.
3 Eugenio Medea Scientific Institute, 23842 Bosisio Parini, Italy.
4 Istituto di Farmacologia e Farmacognosia, University of Urbino "Carlo Bo," 61029 Urbino, Italy.
5 Stem Cell Research Institute, Dipartimento di Biotecnologie, Ospedale San Raffaele, 20132 Milan, Italy.
6 Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK.

* To whom correspondence should be addressed. E-mail: enzo.nisoli{at}unimi.it

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