Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
Author(s)
Type
Journal Article
Abstract
Overexpression of sirtuins (NAD+-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), Caenorhabditis elegans and Drosophila melanogaster1,2,3. Studies of the effects of genes on ageing are vulnerable to confounding effects of genetic background4. 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 overexpression1 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 overexpression2 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 reported3, 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 dependent3. 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.
Date Issued
2011-09-21
Date Acceptance
2011-06-10
Citation
Nature, 2011, 477 (7365), pp.482-U136
ISSN
0028-0836
Publisher
Nature Research
Start Page
482
End Page
U136
Journal / Book Title
Nature
Volume
477
Issue
7365
Copyright Statement
©2011 Macmillan Publishers Limited. All rights reserved. The final publication is available at Springer via https://doi.org/10.1038/nature10296
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000295080500044&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
POSITION-EFFECT VARIEGATION
SMALL-MOLECULE ACTIVATORS
CAENORHABDITIS-ELEGANS
SACCHAROMYCES-CEREVISIAE
DIETARY RESTRICTION
CALORIE RESTRICTION
RESVERATROL
LONGEVITY
SIRTUINS
GENETICS
Publication Status
Published
Date Publish Online
2011-09-21