Sir2 deletion prevents lifespan extension in 32 long-lived mutants.
Authors: 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 Year: 2011 Journal: Aging cell 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 sir2Delta 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 sir2Delta lifespan defect is a rare phenotype among longevity interventions and suggest that sir2Delta 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. Reference
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