Sir2 deletion prevents lifespan extension in 32 long‐lived mutants

Aging Cell

Joe R. Delaney⁵  George L. Sutphin⁵  Ben Dulken⁵  Sylvia Sim⁵  Jin R. Kim⁵  Brett Robison⁴  Jennifer Schleit⁵  Christopher J. Murakami⁵  Daniel Carr⁵  Elroy H. An⁵  Eunice Choi⁴  Annie Chou⁵  Marissa Fletcher⁵  Monika Jelic⁵  Bin Liu¹  Daniel Lockshon⁴  Richard M. Moller⁵  Diana N. Pak⁴  Qi Peng¹  Zhao J. Peng⁵  Kim M. Pham⁴  Michael Sage⁴  Amrita Solanky⁵  Kristan K. Steffen⁴  Mitsuhiro Tsuchiya⁴  Scott Tsuchiyama⁴  Simon Johnson⁵  Chris Raabe⁵  Yousin Suh³  Zhongjun Zhou²  Xinguang Liu¹  Brian K. Kennedy⁴ 

[1] Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan 523808, China;Department of Biochemistry, The University of Hong Kong, Hong Kong, China;Institute of Aging Research, Guangdong Medical College, Dongguan 523808, China;Department of Biochemistry, University of Washington, Seattle, WA, USA;Department of Pathology, University of Washington, Seattle, WA, USA

关键词: ageing;    replicative lifespan;    longevity;    yeast;    epistasis;   

DOI  :  10.1111/j.1474-9726.2011.00742.x

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

Unknown   
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland