The Experts below are selected from a list of 84 Experts worldwide ranked by ideXlab platform
James Jeffrey Mcelwee - One of the best experts on this subject based on the ideXlab platform.
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absence of effects of sir2 overexpression on lifespan in c elegans and Drosophila
Nature, 2011Co-Authors: Camilla Burnett, Martin Goss, Milán Somogyvári, Matthew D. Piper, Matthew Hoddinott, Vid Leko, George L. Sutphin, Filipe Cabreiro, Sara Valentini, James Jeffrey McelweeAbstract:Overexpression of sirtuins has been reported to increase lifespan in Caenorhabditis elegans and Drosophila melanogaster. The effects of dietary restriction on the lifespan of flies have also been reported to be Sir2-dependent. Here it is shown that these findings are attributable to the confounding effects of genetic background. This work suggests that the life-extending effect of sirtuin overexpression may be limited to yeast, and also supports studies in yeast and C. elegans that show that the effects of dietary restriction are not mediated by sirtuins. 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.
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Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
Nature, 2011Co-Authors: Camilla Burnett, Martin Goss, Milán Somogyvári, Matthew D. Piper, Matthew Hoddinott, Vid Leko, George L. Sutphin, Filipe Cabreiro, Sara Valentini, James Jeffrey McelweeAbstract: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.
Camilla Burnett - One of the best experts on this subject based on the ideXlab platform.
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absence of effects of sir2 overexpression on lifespan in c elegans and Drosophila
Nature, 2011Co-Authors: Camilla Burnett, Martin Goss, Milán Somogyvári, Matthew D. Piper, Matthew Hoddinott, Vid Leko, George L. Sutphin, Filipe Cabreiro, Sara Valentini, James Jeffrey McelweeAbstract:Overexpression of sirtuins has been reported to increase lifespan in Caenorhabditis elegans and Drosophila melanogaster. The effects of dietary restriction on the lifespan of flies have also been reported to be Sir2-dependent. Here it is shown that these findings are attributable to the confounding effects of genetic background. This work suggests that the life-extending effect of sirtuin overexpression may be limited to yeast, and also supports studies in yeast and C. elegans that show that the effects of dietary restriction are not mediated by sirtuins. 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.
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Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
Nature, 2011Co-Authors: Camilla Burnett, Martin Goss, Milán Somogyvári, Matthew D. Piper, Matthew Hoddinott, Vid Leko, George L. Sutphin, Filipe Cabreiro, Sara Valentini, James Jeffrey McelweeAbstract: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.
Tomoe Negishi - One of the best experts on this subject based on the ideXlab platform.
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Increase of somatic cell mutations in oxidative damage-sensitive Drosophila
Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 2018Co-Authors: Ryota Koike, Tomoyo Uchiyama, Sakae Arimoto-kobayashi, Keinosuke Okamoto, Tomoe NegishiAbstract:Oxidative damage is an important genotoxic source for almost all organisms. To efficiently detect mutations induced by oxidative damage, we previously developed a urate-null Drosophila Strain. Using this Drosophila Strain, we showed the mutagenic activity of environmental cigarette smoke (ECS) and the herbicide paraquat, which are known to produce reactive oxygen species (ROS). In the present study, we examined the mutagenic activities of carcinogenic mutagens that are considered to cause mutations by adduct formation, alkylation, or crosslinking of cellular DNA in the oxidative damage-sensitive Drosophila to evaluate how the oxidative damage induced by these mutagens is involved in causing mutations. In addition, we evaluated whether these oxidative damage-sensitive flies may be useful for mutation assays. We performed the wing-spot test in oxidative damage-sensitive Drosophila (urate-null Strains) to examine the mutagenicity of 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx), mitomycin C (MMC), 4-nitroquinoline N-oxide (4NQO), N-nitrosodimethyl-amine (NDMA), and N-nitrosodiethylamine (NDEA). We also observed the mutagenicity of X-ray irradiation as a control in which mutations should be mainly caused by oxidative damage. As expected, the mutagenic activity of X-ray irradiation was higher in the urate-null Drosophila than in the wild-type Drosophila. The mutagenic activities of the tested compounds were also higher in the urate-null Drosophila than in the wild-type Drosophila. In experiments using another urate-null Strain, the mutagenicity of N-nitrosodialkylamines was also higher in the urate-null flies than in the wild-type ones. The tested compounds in this study were more mutagenic in urate-null Drosophila than in wild-type Drosophila. It was supposed that ROS were generated and that the ROS might be involved in mutagenesis. The present results support the notion that in addition to causing DNA lesions via adduct formation, alkylation, or DNA crosslinking, these mutagens also cause mutations via ROS-induced DNA damage. As such, urate-null Drosophila appear to be useful for detecting the mutagenic activity of various mutagens, especially those that produce reactive oxygen. If the mutation rate increases on a mutation assay using urate-null Drosophila, it might suggest that the mutagen generates ROS, and that the produced ROS is involved in causing mutations.
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Increase of somatic cell mutations in oxidative damage-sensitive Drosophila
BMC, 2018Co-Authors: Ryota Koike, Tomoyo Uchiyama, Sakae Arimoto-kobayashi, Keinosuke Okamoto, Tomoe NegishiAbstract:Abstract Background Oxidative damage is an important genotoxic source for almost all organisms. To efficiently detect mutations induced by oxidative damage, we previously developed a urate-null Drosophila Strain. Using this Drosophila Strain, we showed the mutagenic activity of environmental cigarette smoke (ECS) and the herbicide paraquat, which are known to produce reactive oxygen species (ROS). In the present study, we examined the mutagenic activities of carcinogenic mutagens that are considered to cause mutations by adduct formation, alkylation, or crosslinking of cellular DNA in the oxidative damage-sensitive Drosophila to evaluate how the oxidative damage induced by these mutagens is involved in causing mutations. In addition, we evaluated whether these oxidative damage-sensitive flies may be useful for mutation assays. Methods We performed the wing-spot test in oxidative damage-sensitive Drosophila (urate-null Strains) to examine the mutagenicity of 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx), mitomycin C (MMC), 4-nitroquinoline N-oxide (4NQO), N-nitrosodimethyl-amine (NDMA), and N-nitrosodiethylamine (NDEA). We also observed the mutagenicity of X-ray irradiation as a control in which mutations should be mainly caused by oxidative damage. Results As expected, the mutagenic activity of X-ray irradiation was higher in the urate-null Drosophila than in the wild-type Drosophila. The mutagenic activities of the tested compounds were also higher in the urate-null Drosophila than in the wild-type Drosophila. In experiments using another urate-null Strain, the mutagenicity of N-nitrosodialkylamines was also higher in the urate-null flies than in the wild-type ones. Conclusions The tested compounds in this study were more mutagenic in urate-null Drosophila than in wild-type Drosophila. It was supposed that ROS were generated and that the ROS might be involved in mutagenesis. The present results support the notion that in addition to causing DNA lesions via adduct formation, alkylation, or DNA crosslinking, these mutagens also cause mutations via ROS-induced DNA damage. As such, urate-null Drosophila appear to be useful for detecting the mutagenic activity of various mutagens, especially those that produce reactive oxygen. If the mutation rate increases on a mutation assay using urate-null Drosophila, it might suggest that the mutagen generates ROS, and that the produced ROS is involved in causing mutations
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the involvement of cell cycle checkpoint mutations in the mutagenesis induced in Drosophila by a longer wavelength light band of solar uv
Photochemical and Photobiological Sciences, 2002Co-Authors: Megumi Toyoshima, Syogo Takinami, Kotaro Hieda, Yoshiya Furusawa, Tomoe NegishiAbstract:Solar ultraviolet radiation is considered to be injurious rather than necessary for most organisms living on the earth. It is reported that the risk of skin cancer in humans increases by the depletion of the ozone layer. We have examined the genotoxicity of solar ultraviolet, especially the longer wavelength light, using Drosophila. Recently, we have demonstrated that light of wavelength up to 340 nm is mutagenic on Drosophila larvae. Using an excision repair-deficient Drosophila Strain (mus201), we have obtained results suggesting that the lesion caused in larvae by the 320 nm-light irradiation may be similar to the damage induced by irradiation at 310 nm, and that light of 330 and 340 nm may induce damage different from that induced by 310 and 320 nm-light. To examine the difference in DNA damage induced by light of a particular wavelength, we performed monochromatic irradiation on larvae of two Drosophila Strains; one excision repair-deficient (mei-9) and another postreplication repair-deficient (mei-41). 310 and 320 nm-light was more mutagenic in the mei-9 Strain than in mei-41, whereas 330 and 340 nm-light was more mutagenic in mei-41 than in mei-9. It is demonstrated that the mei-41 gene is a homologue of the human atm gene which is responsible for a cell cycle checkpoint. This result suggests that 310–320 nm-light induces DNA damage that is subject to nucleotide excision repair (NER) and that 330–360 nm-light causes damage to be recognized by the cell cycle checkpoint but it is not repairable by NER.
Albert Pastink - One of the best experts on this subject based on the ideXlab platform.
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Disruption of Drosophila Rad50 causes pupal lethality, the accumulation of DNA double-strand breaks and the induction of apoptosis in third instar larvae.
DNA repair, 2004Co-Authors: Marcin M. Gorski, Ron J. Romeijn, J.c.j. Eeken, Anja W. M. De Jong, Bert L. Van Veen, Karoly Szuhai, Leon H.f. Mullenders, Wouter Ferro, Albert PastinkAbstract:The Rad50/Mre11/Nbs1 protein complex has a crucial role in DNA metabolism, in particular in double-strand break (DSB) repair through homologous recombination (HR). To elucidate the role of the Rad50 protein complex in DSB repair in a multicellular eukaryote, we generated a Rad50 deficient Drosophila Strain by P-element mediated mutagenesis. Disruption of Rad50 causes retarded development and pupal lethality. To investigate the mechanism of pupal death, brains and wing imaginal discs from third instar larvae were studied in more detail. Wing imaginal discs from Rad50 mutant larvae displayed a 3.5-fold increase in the induction of spontaneous apoptotic cells in comparison to their heterozygous siblings. This finding correlates with increased levels of phosphorylated histone H2Av, indicating an accumulation of DSBs in Rad50 mutant larvae. A 45-fold increase in the frequency of anaphase bridges was detected in the brains of Rad50 deficient larvae, consistent with a role for Rad50 in telomere maintenance and/or replication of DNA. The induction of DSBs and defects in chromosome segregation are in agreement with a role of Drosophila Rad50 in repairing the DSBs that arise during replication.
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targeted inactivation of mouse rad52 reduces homologous recombination but not resistance to ionizing radiation
Molecular and Cellular Biology, 1998Co-Authors: Tonnie Rijkers, Jody Van Den Ouweland, Bruno Morolli, A Rolink, Willy M Baarends, Petra P H Van Sloun, P H M Lohman, Albert PastinkAbstract:Double-strand breaks (DSBs) in the DNA of living organisms occur during several physiological processes including meiotic recombination, mating-type switching in yeast, and V(D)J rearrangement in developing B and T lymphocytes. Agents such as ionizing radiation and certain chemicals also lead to the induction of DSBs in the genome. If left unrepaired, DSBs result in broken chromosomes and cell death, as has been shown convincingly in yeast (5). Alternatively, incorrect repair of DSBs may generate deletions, chromosome rearrangements, and cell transformation and eventually lead to the formation of tumors. Two main pathways are known to be involved in the repair of DSBs in eukaryotes: end-to-end rejoining, a homology-independent but error-prone process, and error-free repair via (homologous) recombination. Repair of DSBs in the yeast Saccharomyces cerevisiae occurs predominantly via recombination, whereas a contribution of end-to-end rejoining can be observed only in a recombination-deficient background (9, 27, 47). Recombinational repair in S. cerevisiae involves the genes of the RAD52 epistasis group, of which nine members have been identified thus far (ScRAD50, ScRAD51, ScRAD52, ScRAD54, ScRAD55, ScRAD57, ScRAD59, ScMRE11, and ScXRS2) (2, 11, 15, 16, 44). Interestingly, it has been shown that ScRAD50, ScMRE11, and ScXRS2 are also involved in end-to-end rejoining (10, 28, 55). Mutations in genes of the RAD52 group result in an increased sensitivity to ionizing radiation and defects in one or more types of recombination. Among these mutants, the Scrad51, Scrad52, and Scrad54 mutants display the most severe radiation sensitivity and defects in recombination. Biochemical experiments with S. cerevisiae have shown that the ScRad51 protein forms nucleoprotein filaments with single-stranded DNA and promotes pairing and limited strand exchange (51). The ScRad52 protein alone or a heterodimer of ScRad55 and ScRad57 functions as a cofactor in this reaction, probably by overcoming the inhibitory effect of replication protein A (32, 45, 49, 50). Recently, ScRad54 has been shown to stimulate the pairing reaction (36). Homologues of most of the RAD52 group genes in S. cerevisiae have been identified in other yeast Strains as well as in higher eukaryotes (1, 15, 26, 30, 35, 53). As in yeast, physical interactions between HsRad51 and HsRad52 and between HsRad51 and HsRad54 proteins have been observed in mammals (17, 42). Moreover, in humans, HsRad51 mediates pairing and strand exchange, which is stimulated by HsRad52 (3, 6). Phenotypic studies of eukaryotic null mutants also suggest that recombination plays a role in the repair of DSBs. Inactivation of the RAD54 homologues in mouse embryonic stem (ES) cells and chicken DT40 B cells increases their sensitivity to ionizing radiation and leads to a decrease in homologous recombination (7, 14). In a Drosophila Strain with mutations in both RAD54 alleles, larval survival was severely affected after X-ray treatment. In addition, the mutant flies were almost completely defective in X-ray-induced mitotic recombination (23). These results imply that the RAD54 homologue in higher eukaryotes plays a role in homologous recombination and in the repair of induced DSBs. A RAD51 null mutation cannot be obtained in chicken DT40 cells or in mouse ES cells, and MmRAD51−/− mouse embryos arrest early in development due to decreased cell proliferation rates and extensive chromosome loss (24, 48, 56). Furthermore, MmRAD51 antisense oligonucleotides significantly inhibit cell growth and increase radiation sensitivity in mouse cells, indicating that the gene is essential for proliferation in vertebrate cells and is involved in the repair of X-ray-induced DNA damage (52). In this paper, inactivation of the homologue of ScRAD52 in the mouse is described. Yeast Scrad52 mutant cells are extremely sensitive to X rays and methyl methanesulfonate (MMS). Repair of DSBs is hardly detectable in these mutants (13). Moreover, Scrad52 Strains are defective in spontaneous and induced mitotic recombination and mating-type switching. The formation of viable spores in meiotically dividing cells is almost completely blocked in a Scrad52-deficient background (15, 16, 44). Using degenerate primers, homologues of ScRAD52 in higher eukaryotes have been identified. The human and mouse proteins, HsRad52 and MmRad52, display about 30% identity to their counterpart from S. cerevisiae (4, 29, 43). The homology is concentrated primarily in the N-terminal region, suggesting an important role in the function of this protein. The highest levels of expression of MmRAD52 were seen in lymphoid organs and testes, suggesting a possible role in recombination and/or cell proliferation (29). In this paper, we describe the effects of inactivation of MmRAD52 on recombination and repair of radiation-induced damage.
George L. Sutphin - One of the best experts on this subject based on the ideXlab platform.
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absence of effects of sir2 overexpression on lifespan in c elegans and Drosophila
Nature, 2011Co-Authors: Camilla Burnett, Martin Goss, Milán Somogyvári, Matthew D. Piper, Matthew Hoddinott, Vid Leko, George L. Sutphin, Filipe Cabreiro, Sara Valentini, James Jeffrey McelweeAbstract:Overexpression of sirtuins has been reported to increase lifespan in Caenorhabditis elegans and Drosophila melanogaster. The effects of dietary restriction on the lifespan of flies have also been reported to be Sir2-dependent. Here it is shown that these findings are attributable to the confounding effects of genetic background. This work suggests that the life-extending effect of sirtuin overexpression may be limited to yeast, and also supports studies in yeast and C. elegans that show that the effects of dietary restriction are not mediated by sirtuins. 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.
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Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
Nature, 2011Co-Authors: Camilla Burnett, Martin Goss, Milán Somogyvári, Matthew D. Piper, Matthew Hoddinott, Vid Leko, George L. Sutphin, Filipe Cabreiro, Sara Valentini, James Jeffrey McelweeAbstract: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.
