Article: Sir2 deletion prevents lifespan extension in 32 long-lived mutants
| Title | Sir2 deletion prevents lifespan extension in 32 long-lived mutants | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Authors | Delaney, JR1 Sutphin, GL1 Dulken, B1 Sim, S1 Kim, JR1 Robison, B1 6 Schleit, J1 Murakami, CJ1 Carr, D1 An, EH1 Choi, E1 Chou, A1 Fletcher, M1 Jelic, M1 Liu, B4 5 Lockshon, D1 6 Moller, RM1 Pak, DN1 Peng, Q4 5 Peng, ZJ1 Pham, KM1 Sage, M1 Solanky, A1 Steffen, KK1 Tsuchiya, M1 6 Tsuchiyama, S1 6 Johnson, S1 Raabe, C1 Suh, Y2 4 Zhou, Z3 Liu, X4 5 Kennedy, BK1 4 6 Kaeberlein, M1 4 | ||||||||||
| Issue Date | 2011 | ||||||||||
| Publisher | Blackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/ACE | ||||||||||
| Citation | Aging Cell, 2011, v. 10 n. 6, p. 1089-1091 [How to Cite?] DOI: http://dx.doi.org/10.1111/j.1474-9726.2011.00742.x | ||||||||||
| 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. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. | ||||||||||
| ISSN | 1474-9718 2011 Impact Factor: 6.265 2011 SCImago Journal Rankings: 0.855 | ||||||||||
| DOI | http://dx.doi.org/10.1111/j.1474-9726.2011.00742.x | ||||||||||
| ISI Accession Number ID | WOS:000297003800018
Funding Information: This work was supported by NIH Grant R01AG025549. JRD, GLS and SJ were supported by NIH Training Grant T32AG000057. JS was supported by NIH Training Grant T32ES007032. XL is supported by The National Natural Science Foundation of China (30672205, 30871440, 30900739, 30971620, 31101051), The Natural Science Foundation of Guangdong Province (7301506, 8452402301001450, 9252402301000002) and Key Foundation of Natural Science Research for Guangdong Universities (06Z015). MK is an Ellison Medical Foundation New Scholar in Aging. | ||||||||||
| References | References in Scopus |
| dc.contributor.author | Delaney, JR | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Sutphin, GL | ||||||||||
| dc.contributor.author | Dulken, B | ||||||||||
| dc.contributor.author | Sim, S | ||||||||||
| dc.contributor.author | Kim, JR | ||||||||||
| dc.contributor.author | Robison, B | ||||||||||
| dc.contributor.author | Schleit, J | ||||||||||
| dc.contributor.author | Murakami, CJ | ||||||||||
| dc.contributor.author | Carr, D | ||||||||||
| dc.contributor.author | An, EH | ||||||||||
| dc.contributor.author | Choi, E | ||||||||||
| dc.contributor.author | Chou, A | ||||||||||
| dc.contributor.author | Fletcher, M | ||||||||||
| dc.contributor.author | Jelic, M | ||||||||||
| dc.contributor.author | Liu, B | ||||||||||
| dc.contributor.author | Lockshon, D | ||||||||||
| dc.contributor.author | Moller, RM | ||||||||||
| dc.contributor.author | Pak, DN | ||||||||||
| dc.contributor.author | Peng, Q | ||||||||||
| dc.contributor.author | Peng, ZJ | ||||||||||
| dc.contributor.author | Pham, KM | ||||||||||
| dc.contributor.author | Sage, M | ||||||||||
| dc.contributor.author | Solanky, A | ||||||||||
| dc.contributor.author | Steffen, KK | ||||||||||
| dc.contributor.author | Tsuchiya, M | ||||||||||
| dc.contributor.author | Tsuchiyama, S | ||||||||||
| dc.contributor.author | Johnson, S | ||||||||||
| dc.contributor.author | Raabe, C | ||||||||||
| dc.contributor.author | Suh, Y | ||||||||||
| dc.contributor.author | Zhou, Z | ||||||||||
| dc.contributor.author | Liu, X | ||||||||||
| dc.contributor.author | Kennedy, BK | ||||||||||
| dc.contributor.author | Kaeberlein, M | ||||||||||
| dc.date.accessioned | 2012-05-29T06:05:14Z | ||||||||||
| dc.date.available | 2012-05-29T06:05:14Z | ||||||||||
| dc.date.issued | 2011 | ||||||||||
| dc.description.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. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. | ||||||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||||||
| dc.identifier.citation | Aging Cell, 2011, v. 10 n. 6, p. 1089-1091 [How to Cite?] DOI: http://dx.doi.org/10.1111/j.1474-9726.2011.00742.x | ||||||||||
| dc.identifier.citeulike | 9760650 | ||||||||||
| dc.identifier.doi | http://dx.doi.org/10.1111/j.1474-9726.2011.00742.x | ||||||||||
| dc.identifier.epage | 1091 | ||||||||||
| dc.identifier.isi | WOS:000297003800018
Funding Information: This work was supported by NIH Grant R01AG025549. JRD, GLS and SJ were supported by NIH Training Grant T32AG000057. JS was supported by NIH Training Grant T32ES007032. XL is supported by The National Natural Science Foundation of China (30672205, 30871440, 30900739, 30971620, 31101051), The Natural Science Foundation of Guangdong Province (7301506, 8452402301001450, 9252402301000002) and Key Foundation of Natural Science Research for Guangdong Universities (06Z015). MK is an Ellison Medical Foundation New Scholar in Aging. | ||||||||||
| dc.identifier.issn | 1474-9718 2011 Impact Factor: 6.265 2011 SCImago Journal Rankings: 0.855 | ||||||||||
| dc.identifier.issue | 6 | ||||||||||
| dc.identifier.pmid | 21902802 | ||||||||||
| dc.identifier.scopus | eid_2-s2.0-81155155530 | ||||||||||
| dc.identifier.spage | 1089 | ||||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/147650 | ||||||||||
| dc.identifier.volume | 10 | ||||||||||
| dc.language | eng | ||||||||||
| dc.publisher | Blackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/ACE | ||||||||||
| dc.publisher.place | United Kingdom | ||||||||||
| dc.relation.ispartof | Aging Cell | ||||||||||
| dc.relation.references | References in Scopus | ||||||||||
| dc.subject.mesh | Dna-Binding Proteins - Deficiency - Genetics | ||||||||||
| dc.subject.mesh | Gene Deletion | ||||||||||
| dc.subject.mesh | Gene Expression Regulation, Fungal | ||||||||||
| dc.subject.mesh | Genotype | ||||||||||
| dc.subject.mesh | Longevity - Genetics | ||||||||||
| dc.subject.mesh | Models, Biological | ||||||||||
| dc.subject.mesh | Observer Variation | ||||||||||
| dc.subject.mesh | Phenotype | ||||||||||
| dc.subject.mesh | Saccharomyces Cerevisiae - Genetics - Metabolism | ||||||||||
| dc.subject.mesh | Saccharomyces Cerevisiae Proteins - Genetics | ||||||||||
| dc.subject.mesh | Silent Information Regulator Proteins, Saccharomyces Cerevisiae - Deficiency - Genetics | ||||||||||
| dc.subject.mesh | Sirtuin 2 - Deficiency - Genetics | ||||||||||
| dc.title | Sir2 deletion prevents lifespan extension in 32 long-lived mutants | ||||||||||
| dc.type | Article |
- University of Washington
- Albert Einstein College of Medicine of Yeshiva University
- The University of Hong Kong
- Guangdong Medical College
- Key Laboratory for Medical Molecular Diagnostics of Guangdong Province
- Buck Institute for Age Research

