Yeast life-span extension by calorie restriction is independent of NAD fluctuation.
Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae, this effect requires Sir2, a conserved NAD+-dependent deacetylase. We report that CR reduces nuclear NAD+ levels in vivo. Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD+:NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR.
Anderson
Rozalyn M
RM
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.
Latorre-Esteves
Magda
M
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.
Neves
Ana Rute
AR
Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Rua da Quinta Grande 6, Apartado 127, 2780-156 OEIRAS, Portugal.
Lavu
Siva
S
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.|Biomol Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, PA 19462, USA.
Medvedik
Oliver
O
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.
Taylor
Christopher
C
Biomol Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, PA 19462, USA.
Howitz
Konrad T
KT
Biomol Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, PA 19462, USA.
Santos
Helena
H
Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Rua da Quinta Grande 6, Apartado 127, 2780-156 OEIRAS, Portugal.
Sinclair
David A
DA
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.
D000079:Acetaldehyde / Q000378:metabolism; D000332:Aerobiosis; D001426:Bacterial Proteins; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D031204:Caloric Restriction; D003470:Culture Media; D004268:DNA-Binding Proteins; D005800:Genes, Fungal; D017930:Genes, Reporter; D006639:Histidine / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism*; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D008136:Longevity; D009682:Magnetic Resonance Spectroscopy; D009243:NAD / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism*; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D023081:CCAAT-Binding Factor; D003470:Culture Media; D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; C061437:HAP4 protein, S cerevisiae; C117105:NadR protein, bacteria; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D014157:Transcription Factors; D009243:NAD; D006639:Histidine; C087778:SIR2 protein, S cerevisiae; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D006836:Hydro-Lyases; C021434:imidazoleglycerolphosphate dehydratase; D000079:Acetaldehyde