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      KCI등재 SCOPUS SCIE

      Do Sirtuins Promote Mammalian Longevity?: A Critical Review on Its Relevance to the Longevity Effect Induced by Calorie Restriction

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      https://www.riss.kr/link?id=A104829022

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      다국어 초록 (Multilingual Abstract)

      Sirtuins (SIRTs), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, are emerging as key molecules that regulate aging and age-related diseases including cancers, metabolic disorders, and neurodegenerative diseases. Seven isoforms of SIRT (SIRT1–7) have been identified in mammals. SIRT1 and 6, mainly localized in the nucleus, regulate transcription of genes and DNA repair. SIRT3 in the mitochondria regulates mitochondrial bioenergetics. Initial studies in yeasts, nematodes, and flies indicated a strong connection of SIRT with the life-prolonging effects of calorie restriction (CR), a robust experimental intervention for longevity in a range of organisms. However, subsequent studies reported controversial findings regarding SIRT roles in the effect of CR. This review describes the functional roles of mammalian SIRTs and discusses their relevance to mechanisms un-derlying the longevity effect of CR.
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      Sirtuins (SIRTs), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, are emerging as key molecules that regulate aging and age-related diseases including cancers, metabolic disorders, and neurodegenerative diseases. Seven isof...

      Sirtuins (SIRTs), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, are emerging as key molecules that regulate aging and age-related diseases including cancers, metabolic disorders, and neurodegenerative diseases. Seven isoforms of SIRT (SIRT1–7) have been identified in mammals. SIRT1 and 6, mainly localized in the nucleus, regulate transcription of genes and DNA repair. SIRT3 in the mitochondria regulates mitochondrial bioenergetics. Initial studies in yeasts, nematodes, and flies indicated a strong connection of SIRT with the life-prolonging effects of calorie restriction (CR), a robust experimental intervention for longevity in a range of organisms. However, subsequent studies reported controversial findings regarding SIRT roles in the effect of CR. This review describes the functional roles of mammalian SIRTs and discusses their relevance to mechanisms un-derlying the longevity effect of CR.

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      참고문헌 (Reference)

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      2 Bernal-Mizrachi, C, "Vascular respiratory uncoupling increases blood pressure and atherosclerosis" 435 : 502-506, 2005

      3 Chen, Y, "Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS" 12 : 534-541, 2011

      4 Imai, S, "Transcriptional silencing and longevity protein Sir2 is an NAD dependent histone deacetylase" 403 : 795-800, 2000

      5 Chen, D, "Tissue-specific regulation of SIRT1 by calorie restriction" 22 : 1753-1757, 2008

      6 Kanfi, Y, "The sirtuin SIRT6 regulates lifespan in male mice" 483 : 218-221, 2012

      7 Yang, B, "The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability" 8 : 2662-2663, 2009

      8 Landry, J, "The silencing protein SIR2 and its homologs are NAD dependent protein deacetylases" 97 : 5807-5811, 2000

      9 Schwer, B, "The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase" 158 : 647-657, 2002

      10 North, B.J, "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase" 11 : 437-444, 2003

      1 Vaziri, H, "hSIR2 (SIRT1) functions as an NAD-dependent p53 deacetylase" 107 : 149-159, 2001

      2 Bernal-Mizrachi, C, "Vascular respiratory uncoupling increases blood pressure and atherosclerosis" 435 : 502-506, 2005

      3 Chen, Y, "Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS" 12 : 534-541, 2011

      4 Imai, S, "Transcriptional silencing and longevity protein Sir2 is an NAD dependent histone deacetylase" 403 : 795-800, 2000

      5 Chen, D, "Tissue-specific regulation of SIRT1 by calorie restriction" 22 : 1753-1757, 2008

      6 Kanfi, Y, "The sirtuin SIRT6 regulates lifespan in male mice" 483 : 218-221, 2012

      7 Yang, B, "The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability" 8 : 2662-2663, 2009

      8 Landry, J, "The silencing protein SIR2 and its homologs are NAD dependent protein deacetylases" 97 : 5807-5811, 2000

      9 Schwer, B, "The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase" 158 : 647-657, 2002

      10 North, B.J, "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase" 11 : 437-444, 2003

      11 Zhong, L, "The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1α" 140 : 280-293, 2010

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      16 Howitz, K.T, "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan" 425 : 191-196, 2003

      17 North, B.J, "Sirtuins: Sir2-related NAD-dependent protein deacetylases of FOXO transcription factors by the SIRT1 deacetylase" 303 : 2011-2015, 2004

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      20 Wood, J.G, "Sirtuin activators mimic caloricrestriction and delay ageing in metazoans" 430 : 686-689, 2004

      21 Kong, X, "Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis" 5 : e11707-, 2010

      22 Hallows, W.C, "Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction" 41 : 139-149, 2011

      23 Someya, S., "Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction" 143 : 802-812, 2010

      24 Sundaresan, N.R, "Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice" 119 : 2758-2771, 2009

      25 Bordone, L, "Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells" 4 : e31-, 2006

      26 Pfluger, P.T, "Sirt1 protects against high-fat diet-induced metabolic damage" 105 : 9793-9798, 2008

      27 Picard, F, "Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma" 429 : 771-776, 2004

      28 Herranz, D, "Sirt1 improves healthy ageing and protects from metabolic syndrome- associated cancer" 1 : 3-, 2010

      29 Li, Y, "SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons" 8 : 38-48, 2008

      30 Kaeberlein, M, "Sir2-independent life span extension by calorie restriction in yeast" 2 : E296-, 2004

      31 Starai, V.J, "Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine" 298 : 2390-2392, 2002

      32 Rogina, B, "Sir2 mediates longevity in the fly through a pathway related to calorie restriction" 101 : 15998-16003, 2004

      33 Daitoku, H, "Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity" 101 : 10042-10047, 2004

      34 Tanner, K.G, "Silent information regulator 2 family of NAD-dependent histone/ protein deacetylases generates a unique product, 1-Oacetyl- ADP-ribose" 97 : 14178-14182, 2000

      35 Pacholec, M, "SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1" 285 : 8340-8351, 2010

      36 Kawahara, T. L., "SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span" 136 : 62-74, 2009

      37 Michishita, E, "SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin" 452 : 492-496, 2008

      38 Nakagawa, T, "SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle" 137 : 560-570, 2009

      39 Nasrin, N, "SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells" 285 : 31995-32002, 2010

      40 Haigis, M.C, "SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic β cells" 126 : 941-954, 2006

      41 Giralt, A, "SIRT3, a pivotal actor in mitochondrial functions: metabolism, cell death and aging" 444 : 1-10, 2012

      42 Shi, T, "SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes" 280 : 13560-13567, 2005

      43 Onyango, P, "SIRT3, a human SIR2 homologue, is an NADdependent deacetylase localized to mitochondria" 99 : 13653-13658, 2002

      44 Green, M.F, "SIRT3 weighs heavily in the metabolic balance: a new role for SIRT3 in metabolic syndrome" 68 : 105-107, 2013

      45 Hirschey, M.D, "SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation" 464 : 121-125, 2010

      46 Yu, W, "SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status" 287 : 14078-14086, 2012

      47 Wang, F, "SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1’s repressive interaction with PPARgamma" 20 : 801-808, 2009

      48 Rothgiesser, K.M, "SIRT2 regulates NF-κB dependent gene expression through deacetylation of p65 Lys310" 123 : 4251-4258, 2010

      49 Bordone, L, "SIRT1 transgenic mice show phenotypes resembling calorie restriction" 6 : 759-767, 2007

      50 Hou, X, "SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase" 283 : 20015-20026, 2008

      51 Mattagajasingh, I, "SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase" 104 : 14855-14860, 2007

      52 Kobayashi, Y, "SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress" 16 : 237-243, 2005

      53 Palacios, J.A, "SIRT1 contributes to telomere maintenance and augments global homologous recombination" 191 : 1299-1313, 2010

      54 Sasaki, T, "Roles of FoxO1 and Sirt1 in the central regulation of food intake" 57 : 939-946, 2010

      55 Dryden, S.C, "Role for human SIRT2 NAD-dependent deace- tylase activity in control of mitotic exit in the cell cycle" 23 : 3173-3185, 2003

      56 Csiszar, A, "Resveratrol induces mitochondrial biogenesis in endothelial cells. Am" 297 : 13-20, 2009

      57 Lagouge, M, "Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha" 127 : 1109-1122, 2006

      58 Pearson, K.J., "Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span" 8 : 157-168, 2008

      59 Lin, S.J, "Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae" 289 : 2126-2128, 2000

      60 Kanfi, Y, "Regulation of SIRT6 protein levels by nutrient availability" 582 : 543-548, 2008

      61 Oemar, B.S, "Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis" 97 : 2494-2498, 1998

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      66 Rodgers, J.T, "Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1" 434 : 113-118, 2005

      67 Nemoto, S, "Nutrient availability regulates SIRT1 through a forkheaddependent pathway" 306 : 2105-2108, 2004

      68 Luo, J, "Negative control of p53 by Sir2α promotes cell survival under stress" 107 : 137-148, 2001

      69 Yeung, F, "Modulation of NF-kappaBdependent transcription and cell survival by the SIRT1 deacetylase" 23 : 2369-2380, 2004

      70 Borra, M.T, "Mechanism of human SIRT1 activation by resveratrol" 280 : 17187-17195, 2005

      71 Ford, E, "Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription" 20 : 1075-1080, 2006

      72 Wang, P, "Loss of AMP-activated protein kinase- α2 impairs the insulin-sensitizing effect of calorie restriction in skeletal muscle" 61 : 1051-1061, 2012

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      74 Bitterman, K.J, "Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1" 277 : 45099-45107, 2002

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      76 Moynihan, K.A, "Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice" 2 : 105-117, 2005

      77 Chen, D, "Increase in activity during calorie restriction requires Sirt1" 310 : 1641-, 2005

      78 Cakir, I, "Hypothalamic Sirt1 regulates food intake in a rodent model system" 4 : 62-74, 2009

      79 Koubova, J, "How does calorie restriction work" 17 : 313-321, 2003

      80 Lamming, D.W, "HST2 mediates SIR2-independent life-span extension by calorie restriction" 309 : 1861-1864, 2005

      81 Fulco, M, "Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt" 14 : 661-673, 2008

      82 Mostoslavsky, R, "Genomic instability and aginglike phenotype in the absence of mammalian SIRT6" 124 : 315-329, 2006

      83 Rine, J, "Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae" 116 : 9-22, 1987

      84 Rodgers, J.T, "Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1" 104 : 12861-12866, 2007

      85 van der Horst, A, "FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2 (SIRT1)" 279 : 28873-28879, 2004

      86 Sinclair, D.A, "Extrachromosomal rDNA circles--a cause of aging in yeast" 91 : 1033-1042, 1997

      87 Michishita, E, "Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins" 16 : 4623-4635, 2005

      88 Fritze, C.E, "Direct evidence for SIR2 modulation of chromatin structure in yeast rDNA" 16 : 6495-6509, 1997

      89 Palacios, O.M, "Diet and exercise signals regulate SIRT3 and activate AMPK and PGC- 1alpha in skeletal muscle" 1 : 771-783, 2009

      90 Borra, M.T, "Conserved enzymatic production and biological effect of O-acetyl-ADP-ribose by silent information regulator 2-like NAD+-dependent deacetylases" 277 : 12632-12641, 2002

      91 Sauve, A.A, "Chemical activation of Sir2-dependent silencing by relief of nicotinamide inhibition" 17 : 595-601, 2005

      92 Michishita, E, "Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6" 8 : 2664-2666, 2009

      93 Qiu, X, "Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation" 12 : 662-667, 2010

      94 Nisoli, E, "Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS" 310 : 314-317, 2005

      95 Cohen, H.Y, "Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase" 305 : 390-392, 2004

      96 Lin, S.J, "Calorie restriction extends yeast life span by lowering the level of NADH" 18 : 12-16, 2004

      97 Hebert, A.S, "Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome" 49 : 186-199, 2013

      98 Dietrich, M.O, "Agrp neurons mediate Sirt1’s action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity" 30 : 11815-11825, 2010

      99 Weed, J.L, "Activity measures in rhesus monkeys on long-term calorie restriction" 62 : 97-103, 1997

      100 Cantó, C, "AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity" 458 : 1056-1060, 2009

      101 Bellizzi, D, "A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages" 85 : 258-263, 2005

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