Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila.
Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila.
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DOI：
10.1038/nature10296
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发表时间：
2011-09-21
期刊：
影响因子：
64.8
通讯作者：
Gems, David
中科院分区：
文献类型：
--
作者：
Burnett, Camilla;Valentini, Sara;Cabreiro, Filipe;Goss, Martin;Somogyvari, Milan;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, Michele;Howard, Ken;Neri, Christian;Bedalov, Antonio;Kaeberlein, Matt;Soti, Csaba;Partridge, Linda;Gems, David
据报道，sirtuins（NAD+依赖性蛋白脱乙酰酶）的过度表达可以增加芽殖酵母、秀丽隐杆线虫和黑腹果蝇的寿命。基因对衰老的影响的研究容易受到遗传背景的干扰。我们重新研究了sirtuin过度表达对衰老的影响，发现遗传背景的标准化和适当控制的使用消除了C。线虫和果蝇。In C.在elegans中，具有高水平sir-2.1过表达的品系的异交废除了寿命增加，但sir-2.1过表达没有废除。相反，长寿与影响感觉神经元的第二位点突变共分离。异交一个低拷贝数sir-2.1过表达的品系也废除了寿命。如前所述，使用UAS-GAL 4系统的dSir 2普遍过表达的果蝇品系相对于野生型对照是长寿的，但相对于适当的转基因对照不是长寿的，并且dSir 2过表达更强的新品系也不是长寿的。这些发现强调了在研究遗传对寿命的影响时，控制遗传背景和转基因插入的诱变效应的重要性。据报道，饮食限制（DR）对果蝇衰老的延长寿命作用也依赖于dSir 2。我们发现，DR增加苍蝇寿命独立的dSir 2。我们的发现并不排除sirtuins在决定后生动物寿命中的作用，但他们确实对先前报道的对C.线虫和果蝇。
Over-expression of sirtuins (NAD+-dependent protein deacetylases) has been reported to increase lifespan in budding yeast, Caenorhabditis elegans and Drosophila melanogaster. Studies of gene effects on ageing are vulnerable to confounding effects of genetic background. We re-examined the reported effects of sirtuin over-expression on ageing and found that standardisation of genetic background and 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 over-expression abrogated the longevity increase, but not sir-2.1 over-expression. Instead, longevity co-segregated with a second-site mutation affecting sensory neurons. Outcrossing of a line with low copy number sir-2.1 over-expression also abrogated longevity. A Drosophila strain with ubiquitous over-expression of dSir2 using the UAS-GAL4 system was long-lived relative to wild-type controls, as previously reported, but not relative to the appropriate transgenic controls, and nor was a new line with stronger over-expression of dSir2. These findings underscore the importance of controlling for genetic background and the mutagenic effects of transgene insertions in studies of genetic effects on lifespan. The life extending effect of dietary restriction (DR) on ageing in Drosophila has also been reported to be dSir2 dependent. We found that DR 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 on lifespan in C. elegans and Drosophila.
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影响因子：
2.7
作者：
HEDGECOCK, EM;CULOTTI, JG;PERKINS, LA
通讯作者：
PERKINS, LA
影响因子：
4.8
作者：
Pacholec, Michelle;Bleasdale, John E.;Ahn, Kay
通讯作者：
Ahn, Kay
影响因子：
3
作者：
Beher, Dirk;Wu, John;Wang, Minghan
通讯作者：
Wang, Minghan
DOI：
10.1146/annurev.pathol.4.110807.092250
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Haigis MC;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
10.5
作者：
Kaeberlein, M;McVey, M;Guarente, L
通讯作者：
Guarente, L