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Sir2 deletion prevents lifespan extension in 32 long-lived mutants.

Activation of Sir2 orthologs is proposed to increase lifespan downstream of dietary restriction. Here, we describe an examination of the effect of 32 different lifespan-extending mutations and four methods of DR on replicative lifespan (RLS) in the short-lived sir2Δ yeast strain. In every case, deletion of SIR2 prevented RLS extension; however, RLS extension was restored when both SIR2 and FOB1 were deleted in several cases, demonstrating that SIR2 is not directly required for RLS extension. These findings indicate that suppression of the sir2Δ lifespan defect is a rare phenotype among longevity interventions and suggest that sir2Δ cells senesce rapidly by a mechanism distinct from that of wild-type cells. They also demonstrate that failure to observe lifespan extension in a short-lived background, such as cells or animals lacking sirtuins, should be interpreted with caution.

Pubmed ID: 21902802


  • Delaney JR
  • Sutphin GL
  • Dulken B
  • Sim S
  • Kim JR
  • Robison B
  • Schleit J
  • Murakami CJ
  • Carr D
  • An EH
  • Choi E
  • Chou A
  • Fletcher M
  • Jelic M
  • Liu B
  • Lockshon D
  • Moller RM
  • Pak DN
  • Peng Q
  • Peng ZJ
  • Pham KM
  • Sage M
  • Solanky A
  • Steffen KK
  • Tsuchiya M
  • Tsuchiyama S
  • Johnson S
  • Raabe C
  • Suh Y
  • Zhou Z
  • Liu X
  • Kennedy BK
  • Kaeberlein M


Aging cell

Publication Data

December 14, 2011

Associated Grants

  • Agency: NIDDK NIH HHS, Id: P60 DK020541
  • Agency: NIA NIH HHS, Id: R01 AG025549
  • Agency: NIA NIH HHS, Id: R01 AG025549-05
  • Agency: NIA NIH HHS, Id: R01AG025549
  • Agency: NIA NIH HHS, Id: T32 AG000057
  • Agency: NIA NIH HHS, Id: T32 AG000057-32
  • Agency: NIEHS NIH HHS, Id: T32 ES007032
  • Agency: NIEHS NIH HHS, Id: T32 ES007032-32
  • Agency: NIA NIH HHS, Id: T32AG000057

Mesh Terms

  • DNA-Binding Proteins
  • Gene Deletion
  • Gene Expression Regulation, Fungal
  • Genotype
  • Longevity
  • Models, Biological
  • Observer Variation
  • Phenotype
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Sirtuin 2