Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.

@article{citeulike:157499, abstract = {Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.}, address = {Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, author = {Anderson, R. M. and Bitterman, K. J. and Wood, J. G. and Medvedik, O. and Sinclair, D. A. }, citeulike-article-id = {157499}, doi = {http://dx.doi.org/10.1038/nature01578}, issn = {0028-0836}, journal = {Nature}, keywords = {lifespan, sir2, sirt1, sirtuin}, month = {May}, number = {6936}, pages = {181--185}, posted-at = {2008-02-14 03:48:23}, priority = {2}, title = {Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.}, url = {http://dx.doi.org/10.1038/nature01578}, volume = {423}, year = {2003} }

TY - JOUR ID - citeulike:157499 L3 - citeulike-article-id:157499 N2 - Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms. IS - 6936 JF - Nature SN - 0028-0836 AD - Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. EP - 185 TI - Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. VL - 423 SP - 181 KW - lifespan KW - sir2 KW - sirt1 KW - sirtuin AU - Anderson, RM AU - Bitterman, KJ AU - Wood, JG AU - Medvedik, O AU - Sinclair, DA PY - 2003/05/08/ UR - http://dx.doi.org/10.1038/nature01578 ER -