Evidence map›Paper›PMID 21938067›Full record

ArticleNature2011

Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila.

Camilla Burnett, Sara Valentini, Filipe Cabreiro, Martin Goss, Milán Somogyvári, Matthew D Piper, Matthew Hoddinott, George L Sutphin, Vid Leko, Joshua J McElwee and 13 more

Open access · greenAbstract read
In one paragraph

Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 322 papers.

0numbers the graph read from it
0cells of the map it votes in
322citing papers in PubMed
25.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

322 citing papers in PubMed, 621 citations in OpenAlex.

  1. Trial
  2. Integrative Approaches to Treating Cellular Senescence in Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  3. Evaluation of Molecular Responses and Longevity Markers inInternational journal of molecular sciences · 2026
    Article
  4. Review
  5. Effect of infant feeding practices on stunting and wasting in Northwest Ethiopia: a birth cohort study.Archives of public health = Archives belges de sante publique · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Potential downsides of calorie restriction.Nature reviews. Endocrinology · 2025
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Regulatory Roles for SIRT1 in Aging and Immunosenescence.Results and problems in cell differentiation · 2025
    Review
  17. Review
  18. Article
  19. Article
  20. Biomolecules · 2024
    Review

262 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 8 institutions in 5 countries.

Camilla BurnettInstitute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK.
Sara Valentini
Filipe Cabreiro
Martin Goss
Milán Somogyvári
Matthew D Piper
Matthew Hoddinott
George L Sutphin
Vid Leko
Joshua J McElwee
Rafael P Vazquez-Manrique
Anne-Marie Orfila
Daniel Ackerman
Catherine Au
Giovanna Vinti
Michèle Riesen
Ken Howard
Christian Neri
Antonio Bedalov
Matt Kaeberlein
Csaba Soti
Linda Partridge
David Gems
University College London · GBMRC Unit for Lifelong Health and Ageing · GBFred Hutch Cancer Center · USSemmelweis University · HUUniversity of Washington · USDélégation Paris 5 · FRInserm · FRUniversité Paris Cité · FR

Funding

GENETIC APPROACHES TO AGING RESEARCHT32AG000057 · NIA · UNIVERSITY OF WASHINGTON · PI RABINOVITCH, PETER S · 1985 to 2019
$14.2M
Mechanisms of Life Span Extension By Dietary DeprivationR01AG031108 · NIA · UNIVERSITY OF WASHINGTON · PI KAEBERLEIN, MATT, VAN GILST, MARC R · 2008 to 2019
$3.2M
Development of cambinol analogues as antilymphoma agentsR01CA129132 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BEDALOV, ANTONIO · 2008 to 2012
$1.8M
NCI NIH HHS CA129132NCI NIH HHS R01 CA129132NIA NIH HHS R01 AG031108NIA NIH HHS R01AG031108NIA NIH HHS T32 AG000057NIA NIH HHS T32AG000057Wellcome Trust 081394
6 · The paper itself

Abstract

Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), Caenorhabditis elegans and Drosophila melanogaster. Studies of the effects of genes on ageing are vulnerable to confounding effects of genetic background. Here we re-examined the reported effects of sirtuin overexpression on ageing and found that standardization of genetic background and the use of appropriate controls abolished the apparent effects in both C. elegans and Drosophila. In C. elegans, outcrossing of a line with high-level sir-2.1 overexpression abrogated the longevity increase, but did not abrogate sir-2.1 overexpression. Instead, longevity co-segregated with a second-site mutation affecting sensory neurons. Outcrossing of a line with low-copy-number sir-2.1 overexpression also abrogated longevity. A Drosophila strain with ubiquitous overexpression of dSir2 using the UAS-GAL4 system was long-lived relative to wild-type controls, as previously reported, but was not long-lived relative to the appropriate transgenic controls, and nor was a new line with stronger overexpression of dSir2. These findings underscore the importance of controlling for genetic background and for the mutagenic effects of transgene insertions in studies of genetic effects on lifespan. The life-extending effect of dietary restriction on ageing in Drosophila has also been reported to be dSir2 dependent. We found that dietary restriction increased fly lifespan independently of dSir2. Our findings do not rule out a role for sirtuins in determination of metazoan lifespan, but they do cast doubt on the robustness of the previously reported effects of sirtuins on lifespan in C. elegans and Drosophila.

Indexed as

AgingAnimalsAnimals, Genetically ModifiedCaenorhabditis elegansCaenorhabditis elegans ProteinsCaloric RestrictionCrosses, GeneticDrosophila melanogasterDrosophila ProteinsFemaleGene ExpressionHistone DeacetylasesLongevityMaleRNA, MessengerSirtuinsCaenorhabditis elegans ProteinsDrosophila ProteinsHistone DeacetylasesRNA, MessengerSIR-2.1 protein, C elegansSirt2 protein, DrosophilaSirtuins

Identifiers

PMID21938067
PMCPMC3188402
OpenAlexW2074974899

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.