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Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila.
Nature. 2011 Sep 21; 477(7365):482-5.Nat

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.

Authors+Show Affiliations

Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21938067

Citation

Burnett, Camilla, et al. "Absence of Effects of Sir2 Overexpression On Lifespan in C. Elegans and Drosophila." Nature, vol. 477, no. 7365, 2011, pp. 482-5.
Burnett C, Valentini S, Cabreiro F, et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature. 2011;477(7365):482-5.
Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvári, M., Piper, M. D., Hoddinott, M., Sutphin, G. L., Leko, V., McElwee, J. J., Vazquez-Manrique, R. P., Orfila, A. M., Ackerman, D., Au, C., Vinti, G., Riesen, M., Howard, K., Neri, C., Bedalov, A., ... Gems, D. (2011). Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature, 477(7365), 482-5. https://doi.org/10.1038/nature10296
Burnett C, et al. Absence of Effects of Sir2 Overexpression On Lifespan in C. Elegans and Drosophila. Nature. 2011 Sep 21;477(7365):482-5. PubMed PMID: 21938067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. AU - Burnett,Camilla, AU - Valentini,Sara, AU - Cabreiro,Filipe, AU - Goss,Martin, AU - Somogyvári,Milán, AU - Piper,Matthew D, AU - Hoddinott,Matthew, AU - Sutphin,George L, AU - Leko,Vid, AU - McElwee,Joshua J, AU - Vazquez-Manrique,Rafael P, AU - Orfila,Anne-Marie, AU - Ackerman,Daniel, AU - Au,Catherine, AU - Vinti,Giovanna, AU - Riesen,Michèle, AU - Howard,Ken, AU - Neri,Christian, AU - Bedalov,Antonio, AU - Kaeberlein,Matt, AU - Soti,Csaba, AU - Partridge,Linda, AU - Gems,David, Y1 - 2011/09/21/ PY - 2010/10/27/received PY - 2011/06/10/accepted PY - 2011/9/23/entrez PY - 2011/9/23/pubmed PY - 2011/11/4/medline SP - 482 EP - 5 JF - Nature JO - Nature VL - 477 IS - 7365 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/21938067/Absence_of_effects_of_Sir2_overexpression_on_lifespan_in_C__elegans_and_Drosophila_ L2 - https://doi.org/10.1038/nature10296 DB - PRIME DP - Unbound Medicine ER -