Sir2 deletion prevents lifespan extension in 32 long-lived mutants

Joe R. Delaney, George L. Sutphin, Ben Dulken, Sylvia Sim, Jin R. Kim, Brett Robison, Jennifer Schleit, Christopher J. Murakami, Daniel Carr, Elroy H. An, Eunice Choi, Annie Chou, Marissa Fletcher, Monika Jelic, Bin Liu, Daniel Lockshon, Richard M. Moller, Diana N. Pak, Qi Peng, Zhao J. PengKim M. Pham, Michael Sage, Amrita Solanky, Kristan K. Steffen, Mitsuhiro Tsuchiya, Scott Tsuchiyama, Simon Johnson, Chris Raabe, Yousin Suh, Zhongjun Zhou, Xinguang Liu, Brian K. Kennedy, Matt Kaeberlein

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1089-1091
Number of pages3
JournalAging cell
Volume10
Issue number6
DOIs
StatePublished - Dec 2011

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Keywords

  • Ageing
  • Epistasis
  • Longevity
  • Replicative lifespan
  • Yeast

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Delaney, J. R., Sutphin, G. L., Dulken, B., Sim, S., Kim, J. R., Robison, B., Schleit, J., Murakami, C. J., Carr, D., An, E. H., Choi, E., Chou, A., Fletcher, M., Jelic, M., Liu, B., Lockshon, D., Moller, R. M., Pak, D. N., Peng, Q., ... Kaeberlein, M. (2011). Sir2 deletion prevents lifespan extension in 32 long-lived mutants. Aging cell, 10(6), 1089-1091. https://doi.org/10.1111/j.1474-9726.2011.00742.x