Abstract:
: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.
journal_name
Celljournal_title
Cellauthors
Fabrizio P,Gattazzo C,Battistella L,Wei M,Cheng C,McGrew K,Longo VDdoi
10.1016/j.cell.2005.08.042subject
Has Abstractpub_date
2005-11-18 00:00:00pages
655-67issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(05)00913-Xjournal_volume
123pub_type
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