The Experts below are selected from a list of 24822 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 Contentious History of Sirtuin Debates
Rambam Maimonides medical journal, 2012Co-Authors: Shoshana Naiman, Haim Y CohenAbstract:The Sirtuins are highly conserved enzyme homologues of the yeast Sir2, with activities of NAD+ dependent deacetylase and/or mono ADP ribosyltransferase. A long line of evidence has implicated Sirtuins in regulating the aging process of yeast, worms, flies, and rodents. Moreover, much work has been published on the important role of Sirtuins in several age-related diseases such as diabetes type II, cancer, cardiovascular diseases, and dyslipidemia. However, despite the many publications supporting a pro-longevity role for Sirtuins, there has been emerging debate about the direct role of Caenorhabditis elegans and Drosophila melanogaster Sirtuins in aging and in lifespan extension in response to dietary restriction. In addition, until recently, the role of the seven mammalian Sirtuins, SIRT1 to SIRT7, in regulating lifespan was unclear. Here, we review the history of the scientific debate on the role of Sirtuins in regulating lifespan, especially in light of a recent publication showing a direct regulation of mammalian lifespan by a Sirtuin family member, SIRT6.
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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.
John M. Denu - One of the best experts on this subject based on the ideXlab platform.
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Sirtuin catalysis and regulation.
The Journal of biological chemistry, 2012Co-Authors: Jessica L. Feldman, Kristin E. Dittenhafer-reed, John M. DenuAbstract:Sirtuins are a family of NAD(+)-dependent protein deacetylases/deacylases that dynamically regulate transcription, metabolism, and cellular stress response. Their general positive link with improved health span in mammals, potential regulation of pathways mediated by caloric restriction, and growing links to human disease have spurred interest in therapeutics that target their functions. Here, we review the current understanding of the chemistry of catalysis, biological targets, and endogenous regulation of Sirtuin activity. We discuss recent efforts to generate small-molecule regulators of Sirtuin activity.
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Mechanisms and Molecular Probes of Sirtuins
Chemistry & biology, 2008Co-Authors: Brian C. Smith, William C. Hallows, John M. DenuAbstract:Sirtuins are critical regulators of many cellular processes, including insulin secretion, the cell cycle, and apoptosis. Sirtuins are associated with a variety of age-associated diseases such as type II diabetes, obesity, and Alzheimer's disease. A thorough understanding of Sirtuin chemical mechanisms will aid toward developing novel therapeutics that regulate metabolic disorders and combat associated diseases. In this review, we discuss the unique deacetylase mechanism of Sirtuins and how this information might be employed to develop inhibitors and other molecular probes for therapeutic and basic research applications. We also cover physiological regulation of Sirtuin activity and how these modes of regulation may be exploited to manipulate Sirtuin activity in live cells. Development of molecular probes and drugs that specifically target Sirtuins will further understanding of Sirtuin biology and potentially afford new treatments of several human diseases.
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the Sirtuin family therapeutic targets to treat diseases of aging
Current Opinion in Chemical Biology, 2008Co-Authors: Jill C Milne, John M. DenuAbstract:Sirtuins have emerged as therapeutic targets to treat age-related diseases. There are seven human Sirtuins (SIRT1-7) that display diversity in cellular localization and function. Growing evidence suggests that small-molecule activators of SIRT1 may counteract age-related afflictions such as type 2 diabetes. Alternatively, inhibitors of SIRT2 may be useful in the treatment of neurodegenerative diseases such as Parkinson's disease. Recent discoveries of small-molecule and protein modulators of Sirtuin deacetylation activity have provided enormous insight into the biological and molecular functions of Sirtuins and have validated their potential as therapeutics.
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Sirtuins Caught in the Act
Structure (London England : 1993), 2006Co-Authors: Brian C. Smith, John M. DenuAbstract:Sirtuins catalyze the NAD + -dependent protein deacetylation of lysine residues. In this issue of Structure , Hoff et al. (2006) report the structure of a Sirtuin homolog with both substrates bound, providing new insight into the catalytic mechanism.
Gail Amir - 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.
Victoria Peshti - 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.