Sir2 blocks extreme life-span extension.
Sir2 is a conserved deacetylase that modulates life span in yeast, worms, and flies and stress response in mammals. In yeast, Sir2 is required for maintaining replicative life span, and increasing Sir2 dosage can delay replicative aging. We address the role of Sir2 in regulating chronological life span in yeast. Lack of Sir2 along with calorie restriction and/or mutations in the yeast AKT homolog, Sch9, or Ras pathways causes a dramatic chronological life-span extension. Inactivation of Sir2 causes uptake and catabolism of ethanol and upregulation of many stress-resistance and sporulation genes. These changes while sufficient to extend chronological life span in wild-type yeast require severe calorie restriction or additional mutations to extend life span of sir2Delta mutants. Our results demonstrate that effects of SIR2 on chronological life span are opposite to replicatve life span and suggest that the relevant activities of Sir2-like deacetylases may also be complex in higher eukaryotes.
Fabrizio
Paola
P
Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA.
Gattazzo
Cristina
C
Battistella
Luisa
L
Wei
Min
M
Cheng
Chao
C
McGrew
Kristen
K
Longo
Valter D
VD
D000262:Adenylyl Cyclases / Q000235:genetics; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D004260:DNA Repair; D015536:Down-Regulation / Q000235:genetics; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress; D011494:Protein Kinases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics; D024483:Vitamin K 3 / Q000494:pharmacology
D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D000431:Ethanol; D024483:Vitamin K 3; D006861:Hydrogen Peroxide; D000426:Alcohol Dehydrogenase; D011494:Protein Kinases; C071569:SCH9 protein kinase; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D000262:Adenylyl Cyclases