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, Rafael P. Vazquez-Manrique, Anne Marie Orfila, Daniel Ackerman, Catherine Au, Giovanna Vinti, Michèle Riesen, Ken Howard, Christian Neri, Antonio Bedalov, Matt Kaeberlein & 3 others C. Söti, Linda Partridge, David Gems

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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.

Original languageEnglish
Pages (from-to)482-485
Number of pages4
JournalNature
Volume477
Issue number7365
DOIs
Publication statusPublished - Sep 22 2011

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Sirtuins
Caenorhabditis elegans
Drosophila
Saccharomycetales
Sensory Receptor Cells
Drosophila melanogaster
Transgenes
Diptera
NAD
Saccharomyces cerevisiae
Mutation
Genes
Genetic Background
Proteins

ASJC Scopus subject areas

  • General

Cite this

Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvári, M., Piper, M. D., ... Gems, D. (2011). Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature, 477(7365), 482-485. https://doi.org/10.1038/nature10296

Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. / Burnett, Camilla; Valentini, Sara; Cabreiro, Filipe; Goss, Martin; Somogyvári, Milán; Piper, Matthew D.; Hoddinott, Matthew; Sutphin, George L.; Leko, Vid; McElwee, Joshua J.; Vazquez-Manrique, Rafael P.; Orfila, Anne Marie; Ackerman, Daniel; Au, Catherine; Vinti, Giovanna; Riesen, Michèle; Howard, Ken; Neri, Christian; Bedalov, Antonio; Kaeberlein, Matt; Söti, C.; Partridge, Linda; Gems, David.

In: Nature, Vol. 477, No. 7365, 22.09.2011, p. 482-485.

Research output: Contribution to journalArticle

Burnett, C, Valentini, S, Cabreiro, F, Goss, M, Somogyvári, M, Piper, MD, Hoddinott, M, Sutphin, GL, Leko, V, McElwee, JJ, Vazquez-Manrique, RP, Orfila, AM, Ackerman, D, Au, C, Vinti, G, Riesen, M, Howard, K, Neri, C, Bedalov, A, Kaeberlein, M, Söti, C, Partridge, L & Gems, D 2011, 'Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila', Nature, vol. 477, no. 7365, pp. 482-485. https://doi.org/10.1038/nature10296
Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvári M, Piper MD et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature. 2011 Sep 22;477(7365):482-485. https://doi.org/10.1038/nature10296
Burnett, Camilla ; Valentini, Sara ; Cabreiro, Filipe ; Goss, Martin ; Somogyvári, Milán ; Piper, Matthew D. ; Hoddinott, Matthew ; Sutphin, George L. ; Leko, Vid ; McElwee, Joshua J. ; Vazquez-Manrique, Rafael P. ; Orfila, Anne Marie ; Ackerman, Daniel ; Au, Catherine ; Vinti, Giovanna ; Riesen, Michèle ; Howard, Ken ; Neri, Christian ; Bedalov, Antonio ; Kaeberlein, Matt ; Söti, C. ; Partridge, Linda ; Gems, David. / Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. In: Nature. 2011 ; Vol. 477, No. 7365. pp. 482-485.
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AU - Piper, Matthew D.

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