The Experts below are selected from a list of 188262 Experts worldwide ranked by ideXlab platform
Haim Y Cohen - One of the best experts on this subject based on the ideXlab platform.
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the sirtuin sirt6 regulates Lifespan in male mice
Nature, 2012Co-Authors: Yariv Kanfi, Shoshana Naiman, Victoria Peshti, Guy Zinman, Liat Nahum, Ziv Barjoseph, Gail Amir, Haim Y CohenAbstract:The role of sirtuins in longevity is controversial, and little is known about mammalian sirtuins; now, male mice that overexpress SIRT6 are shown to have a longer Lifespan than wild-type mice, unlike their female counterparts. The role of sirtuin deacetylases in the regulation of Lifespan of lower organisms is controversial, and the roles of many of the mammalian sirtuins, SIRT1 to SIRT7, in regulating Lifespan are unclear. Here, Haim Cohen and colleagues show that transgenic male — but not female — mice overexpressing exogenous Sirt6 have a significantly longer Lifespan than their wild-type littermates. The authors conclude that SIRT6 is an important regulator of mammalian longevity, and they raise the prospect that it might be possible to manipulate SIRT6 levels to treat age-related diseases. The significant increase in human Lifespan during the past century confronts us with great medical challenges. To meet these challenges, the mechanisms that determine healthy ageing must be understood and controlled. Sirtuins are highly conserved deacetylases that have been shown to regulate Lifespan in yeast, nematodes and fruitflies1. However, the role of sirtuins in regulating worm and fly Lifespan has recently become controversial2. Moreover, the role of the seven mammalian sirtuins, SIRT1 to SIRT7 (homologues of the yeast sirtuin Sir2), in regulating Lifespan is unclear3. Here we show that male, but not female, transgenic mice overexpressing Sirt6 (ref. 4) have a significantly longer Lifespan than wild-type mice. Gene expression analysis revealed significant differences between male Sirt6-transgenic mice and male wild-type mice: transgenic males displayed lower serum levels of insulin-like growth factor 1 (IGF1), higher levels of IGF-binding protein 1 and altered phosphorylation levels of major components of IGF1 signalling, a key pathway in the regulation of Lifespan5. This study shows the regulation of mammalian Lifespan by a sirtuin family member and has important therapeutic implications for age-related diseases.
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The sirtuin SIRT6 regulates Lifespan in male mice
Nature, 2012Co-Authors: Yariv Kanfi, Shoshana Naiman, Victoria Peshti, Guy Zinman, Liat Nahum, Ziv Bar-joseph, Gail Amir, Haim Y CohenAbstract:The significant increase in human Lifespan during the past century confronts us with great medical challenges. To meet these challenges, the mechanisms that determine healthy ageing must be understood and controlled. Sirtuins are highly conserved deacetylases that have been shown to regulate Lifespan in yeast, nematodes and fruitflies. However, the role of sirtuins in regulating worm and fly Lifespan has recently become controversial. Moreover, the role of the seven mammalian sirtuins, SIRT1 to SIRT7 (homologues of the yeast sirtuin Sir2), in regulating Lifespan is unclear. Here we show that male, but not female, transgenic mice overexpressing Sirt6 (ref. 4) have a significantly longer Lifespan than wild-type mice. Gene expression analysis revealed significant differences between male Sirt6-transgenic mice and male wild-type mice: transgenic males displayed lower serum levels of insulin-like growth factor 1 (IGF1), higher levels of IGF-binding protein 1 and altered phosphorylation levels of major components of IGF1 signalling, a key pathway in the regulation of Lifespan. This study shows the regulation of mammalian Lifespan by a sirtuin family member and has important therapeutic implications for age-related diseases.
Yariv Kanfi - One of the best experts on this subject based on the ideXlab platform.
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the sirtuin sirt6 regulates Lifespan in male mice
Nature, 2012Co-Authors: Yariv Kanfi, Shoshana Naiman, Victoria Peshti, Guy Zinman, Liat Nahum, Ziv Barjoseph, Gail Amir, Haim Y CohenAbstract:The role of sirtuins in longevity is controversial, and little is known about mammalian sirtuins; now, male mice that overexpress SIRT6 are shown to have a longer Lifespan than wild-type mice, unlike their female counterparts. The role of sirtuin deacetylases in the regulation of Lifespan of lower organisms is controversial, and the roles of many of the mammalian sirtuins, SIRT1 to SIRT7, in regulating Lifespan are unclear. Here, Haim Cohen and colleagues show that transgenic male — but not female — mice overexpressing exogenous Sirt6 have a significantly longer Lifespan than their wild-type littermates. The authors conclude that SIRT6 is an important regulator of mammalian longevity, and they raise the prospect that it might be possible to manipulate SIRT6 levels to treat age-related diseases. The significant increase in human Lifespan during the past century confronts us with great medical challenges. To meet these challenges, the mechanisms that determine healthy ageing must be understood and controlled. Sirtuins are highly conserved deacetylases that have been shown to regulate Lifespan in yeast, nematodes and fruitflies1. However, the role of sirtuins in regulating worm and fly Lifespan has recently become controversial2. Moreover, the role of the seven mammalian sirtuins, SIRT1 to SIRT7 (homologues of the yeast sirtuin Sir2), in regulating Lifespan is unclear3. Here we show that male, but not female, transgenic mice overexpressing Sirt6 (ref. 4) have a significantly longer Lifespan than wild-type mice. Gene expression analysis revealed significant differences between male Sirt6-transgenic mice and male wild-type mice: transgenic males displayed lower serum levels of insulin-like growth factor 1 (IGF1), higher levels of IGF-binding protein 1 and altered phosphorylation levels of major components of IGF1 signalling, a key pathway in the regulation of Lifespan5. This study shows the regulation of mammalian Lifespan by a sirtuin family member and has important therapeutic implications for age-related diseases.
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The sirtuin SIRT6 regulates Lifespan in male mice
Nature, 2012Co-Authors: Yariv Kanfi, Shoshana Naiman, Victoria Peshti, Guy Zinman, Liat Nahum, Ziv Bar-joseph, Gail Amir, Haim Y CohenAbstract:The significant increase in human Lifespan during the past century confronts us with great medical challenges. To meet these challenges, the mechanisms that determine healthy ageing must be understood and controlled. Sirtuins are highly conserved deacetylases that have been shown to regulate Lifespan in yeast, nematodes and fruitflies. However, the role of sirtuins in regulating worm and fly Lifespan has recently become controversial. Moreover, the role of the seven mammalian sirtuins, SIRT1 to SIRT7 (homologues of the yeast sirtuin Sir2), in regulating Lifespan is unclear. Here we show that male, but not female, transgenic mice overexpressing Sirt6 (ref. 4) have a significantly longer Lifespan than wild-type mice. Gene expression analysis revealed significant differences between male Sirt6-transgenic mice and male wild-type mice: transgenic males displayed lower serum levels of insulin-like growth factor 1 (IGF1), higher levels of IGF-binding protein 1 and altered phosphorylation levels of major components of IGF1 signalling, a key pathway in the regulation of Lifespan. This study shows the regulation of mammalian Lifespan by a sirtuin family member and has important therapeutic implications for age-related diseases.
Michael Breitenbach - One of the best experts on this subject based on the ideXlab platform.
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A novel assay for replicative Lifespan in Saccharomyces cerevisiae
FEMS yeast research, 2004Co-Authors: Stefanie Jarolim, Jonathan I. Millen, Gino Heeren, Peter Laun, David S. Goldfarb, Michael BreitenbachAbstract:The replicative Lifespan of Saccharomyces cerevisiae is determined by both genetic and environmental factors. Many of the same factors determine the Lifespan of metazoan animals. The lack of fast and reliable Lifespan assays has limited the pace of yeast aging research. In this study we describe a novel strategy for assaying replicative Lifespan in yeast, and apply it in a screening of mutants that are resistant to pro-oxidants. The assay reproduces the Lifespan-shortening effects of deleting SIR2 and of growth in the presence of paraquat, a pro-oxidant. The Lifespan-increasing activity of resveratrol is also reproduced. Compared to current assays, this new strategy promises to significantly increase the possible number of replicative-Lifespan determinations.
Ronny C. Woodruff - One of the best experts on this subject based on the ideXlab platform.
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Somatic movement of the manner transposable element and Lifespan of Drosophila species
Mutation Research\ dnaging, 1995Co-Authors: Alexey G. Nikitin, Ronny C. WoodruffAbstract:Abstract The effect of somatic movement of the mariner transposable element on Lifespan was measured in Drosophila simulans and Drosophila melanogaster males at 25°C. In D. simulans this movement significantly decreased Lifespan, whereas in D. melanogaster no correlation between transposon movement and Lifespan was found. The results in D. Simulans support the hypothesis that somatic genetic damage induced by DNA element movement can reduce Lifespan.
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Somatic movement of the mariner transposable element and Lifespan of Drosophila species.
Mutation research, 1995Co-Authors: Alexey G. Nikitin, Ronny C. WoodruffAbstract:The effect of somatic movement of the mariner transposable element on Lifespan was measured in Drosophila simulans and Drosophila melanogaster males at 25 degrees C. In D. simulans this movement significantly decreased Lifespan, whereas in D. melanogaster no correlation between transposon movement and Lifespan was found. The results in D. simulans support the hypothesis that somatic genetic damage induced by DNA element movement can reduce Lifespan.
Anne Brunet - One of the best experts on this subject based on the ideXlab platform.
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mono unsaturated fatty acids link h3k4me3 modifiers to c elegans Lifespan
Nature, 2017Co-Authors: Elizabeth A Schroeder, Katja Hebestreit, Carlos G Silvagarcia, William B Mair, Anne BrunetAbstract:Chromatin and metabolic states both influence Lifespan, but how they interact in Lifespan regulation is largely unknown. The COMPASS chromatin complex, which trimethylates lysine 4 on histone H3 (H3K4me3), regulates Lifespan in Caenorhabditis elegans. However, the mechanism by which H3K4me3 modifiers affect longevity, and whether this mechanism involves metabolic changes, remain unclear. Here we show that a deficiency in H3K4me3 methyltransferase, which extends Lifespan, promotes fat accumulation in worms with a specific enrichment of mono-unsaturated fatty acids (MUFAs). This fat metabolism switch in H3K4me3 methyltransferase-deficient worms is mediated at least in part by the downregulation of germline targets, including S6 kinase, and by the activation of an intestinal transcriptional network that upregulates delta-9 fatty acid desaturases. Notably, the accumulation of MUFAs is necessary for the Lifespan extension of H3K4me3 methyltransferase-deficient worms, and dietary MUFAs are sufficient to extend Lifespan. Given the conservation of lipid metabolism, dietary or endogenous MUFAs could extend Lifespan and healthspan in other species, including mammals. A deficiency in H3K4me3 methyltransferase causes accumulation of mono-unsaturated fatty acids, which is important for Lifespan extension in C. elegans and could be relevant in mammals. The Lifespan of a worm is extended by H3K4me3 methyltransferase deficiency, but how and why remains unclear. Here it is shown that the loss of H3K4me3 in the germline affects fat metabolism in the worm intestine, resulting in the accumulation of mono-unsaturated fatty acids (MUFAs), but not poly-unsaturated fatty acids (PUFAs). The fat switch appears to be mediated in part by the downregulation of specific targets in the germline, including S6K, and the activation of a transcriptional network in the intestine leading to the upregulation of conserved delta-9 fatty acid desaturases. MUFA accumulation is necessary for the increased longevity caused by H3K4me3-methyltransferase deficiency, and the authors found that dietary MUFAs, but not PUFAs, were sufficient to extend worm Lifespan. Whether dietary or endogenous MUFAs could extend Lifespan and healthspan in other species remains to be seen.
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Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans Lifespan
Nature, 2017Co-Authors: Shuo Han, Carlos G. Silva-garcía, Katja Hebestreit, Elizabeth A Schroeder, William B Mair, Anne BrunetAbstract:Chromatin and metabolic states both influence Lifespan, but how they interact in Lifespan regulation is largely unknown. The COMPASS chromatin complex, which trimethylates lysine 4 on histone H3 (H3K4me3), regulates Lifespan in Caenorhabditis elegans. However, the mechanism by which H3K4me3 modifiers affect longevity, and whether this mechanism involves metabolic changes, remain unclear. Here we show that a deficiency in H3K4me3 methyltransferase, which extends Lifespan, promotes fat accumulation in worms with a specific enrichment of mono-unsaturated fatty acids (MUFAs). This fat metabolism switch in H3K4me3 methyltransferase-deficient worms is mediated at least in part by the downregulation of germline targets, including S6 kinase, and by the activation of an intestinal transcriptional network that upregulates delta-9 fatty acid desaturases. Notably, the accumulation of MUFAs is necessary for the Lifespan extension of H3K4me3 methyltransferase-deficient worms, and dietary MUFAs are sufficient to extend Lifespan. Given the conservation of lipid metabolism, dietary or endogenous MUFAs could extend Lifespan and healthspan in other species, including mammals.
