title: Sir2 deletion prevents lifespan extension in 32 long-lived mutants.
abstract: 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.
authors: Department of Pathology, University of Washington, Seattle, WA, USA.
authors: Joe R
authors: JR
authors: Delaney
authors: George L
authors: GL
authors: Sutphin
authors: Ben
authors: B
authors: Dulken
authors: Sylvia
authors: S
authors: Sim
authors: Jin R
authors: JR
authors: Kim
authors: Brett
authors: B
authors: Robison
authors: Jennifer
authors: J
authors: Schleit
authors: Christopher J
authors: CJ
authors: Murakami
authors: Daniel
authors: D
authors: Carr
authors: Elroy H
authors: EH
authors: An
authors: Eunice
authors: E
authors: Choi
authors: Annie
authors: A
authors: Chou
authors: Marissa
authors: M
authors: Fletcher
authors: Monika
authors: M
authors: Jelic
authors: Bin
authors: B
authors: Liu
authors: Daniel
authors: D
authors: Lockshon
authors: Richard M
authors: RM
authors: Moller
authors: Diana N
authors: DN
authors: Pak
authors: Qi
authors: Q
authors: Peng
authors: Zhao J
authors: ZJ
authors: Peng
authors: Kim M
authors: KM
authors: Pham
authors: Michael
authors: M
authors: Sage
authors: Amrita
authors: A
authors: Solanky
authors: Kristan K
authors: KK
authors: Steffen
authors: Mitsuhiro
authors: M
authors: Tsuchiya
authors: Scott
authors: S
authors: Tsuchiyama
authors: Simon
authors: S
authors: Johnson
authors: Chris
authors: C
authors: Raabe
authors: Yousin
authors: Y
authors: Suh
authors: Zhongjun
authors: Z
authors: Zhou
authors: Xinguang
authors: X
authors: Liu
authors: Brian K
authors: BK
authors: Kennedy
authors: Matt
authors: M
authors: Kaeberlein
mesh_terms: D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D008136:Longevity / Q000235:genetics*; D008954:Models, Biological; D015588:Observer Variation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000172:deficiency / Q000235:genetics*; D056565:Sirtuin 2 / Q000172:deficiency / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C105579:FOB1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2