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Cited by 2,085Sirtuins and Resveratrol in MedicineGenetics, Aging, and Longevity in Model OrganismsNuclear Receptors and Signaling

Mammalian Sirtuins: Biological Insights and Disease Relevance

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Haigis, Marcia C., Sinclair, David A.·2010·Annual Review of Pathology: Mechanisms of Disease
DOI 10.1146/annurev.pathol.4.110807.092250PMC PMC2866163
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Abstract

Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years.

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  1. [1]Sinclair DA Guarente L Extrachromosomal rDNA circles—a cause of aging in yeast Cell 1997 91 1033 1042 9428525
  2. [3]Sinclair DA Guarente L Unlocking the secrets of longevity genes Sci. Am 2006 294 48 57 16502611
  3. [5]Westphal CH Dipp MA Guarente L A therapeutic role for sirtuins in diseases of aging? Trends Biochem. Sci 2007 32 555 560 17980602
  4. [6]Frye RA Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity Biochem. Biophys. Res. Commun 1999 260 273 279 10381378
  5. [7]Smith JS Boeke JD An unusual form of transcriptional silencing in yeast ribosomal DNA Genes Dev 1997 11 241 254 9009206
  6. [8]Bryk M Banerjee M Murphy M Knudsen KE Garfinkel DJ Curcio MJ Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast Genes Dev 1997 11 255 269 9009207
  7. [9]Aguilaniu H Gustafsson L Rigoulet M Nystrom T Asymmetric inheritance of oxidatively damaged proteins during cytokinesis Science 2003 299 1751 1753 12610228
  8. [10]North BJ Verdin E Sirtuins: Sir2-related NAD-dependent protein deacetylases Genome Biol 2004 5 224 15128440 PMC416462
  9. [11]Tissenbaum HA Guarente L Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans Nature 2001 410 227 230 11242085
  10. [12]Wang Y Tissenbaum HA Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO Mech. Ageing Dev 2006 127 48 56 16280150
  11. [13]Rogina B Helfand SL Sir2 mediates longevity in the fly through a pathway related to calorie restriction Proc. Natl. Acad. Sci. USA 2004 101 15998 16003 15520384 PMC528752
  12. [14]Frye RA Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins Biochem. Biophys. Res. Commun 2000 273 793 798 10873683
  13. [15]Haigis MC Guarente LP Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction Genes Dev 2006 20 2913 2921 17079682
  14. [16]Tsang AW Escalante-Semerena JC CobB, a new member of the SIR2 family of eucaryotic regulatory proteins, is required to compensate for the lack of nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase activity in cobT mutants during cobalamin biosynthesis in Salmonella typhimurium LT2 J. Biol. Chem 1998 273 31788 31794 9822644
  15. [17]North BJ Marshall BL Borra MT Denu JM Verdin E The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase Mol. Cell 2003 11 437 444 12620231
  16. [18]Tanner KG Landry J Sternglanz R Denu JM Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose Proc. Natl. Acad. Sci. USA 2000 97 14178 14182 11106374 PMC18891
  17. [19]Landry J Slama JT Sternglanz R Role of NAD+ in the deacetylase activity of the SIR2-like proteins Biochem. Biophys. Res. Commun 2000 278 685 690 11095969
  18. [21]Haigis MC Mostoslavsky R Haigis KM Fahie K Christodoulou DC SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic β cells Cell 2006 126 941 954 16959573
  19. [23]Tanny JC Dowd GJ Huang J Hilz H Moazed D An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing Cell 1999 99 735 745 10619427
  20. [24]Moazed D Enzymatic activities of Sir2 and chromatin silencing Curr. Opin. Cell Biol 2001 13 232 238 11248558
  21. [25]Sauve AA Celic I Avalos J Deng H Boeke JD Schramm VL Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactions Biochemistry 2001 40 15456 15463 11747420
  22. [26]Schmidt MT Smith BC Jackson MD Denu JM Coenzyme specificity of Sir2 protein deacetylases: implications for physiological regulation J. Biol. Chem 2004 279 40122 40129 15269219
  23. [27]Borra MT Langer MR Slama JT Denu JM Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases Biochemistry 2004 43 9877 9887 15274642
  24. [28]Sauve AA Pharmaceutical strategies for activating sirtuins Curr. Pharm. Des 2009 15 45 56 19149602
  25. [29]Smith BC Hallows WC Denu JM Mechanisms and molecular probes of sirtuins Chem. Biol 2008 15 1002 1013 18940661 PMC2626554
  26. [30]Sauve AA Wolberger C Schramm VL Boeke JD The biochemistry of sirtuins Annu. Rev. Biochem 2006 75 435 465 16756498
  27. [31]Bitterman KJ Anderson RM Cohen HY Latorre-Esteves M Sinclair DA Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1 J. Biol. Chem 2002 277 45099 45107 12297502
  28. [32]Sauve AA Moir RD Schramm VL Willis IM Chemical activation of Sir2-dependent silencing by relief of nicotinamide inhibition Mol. Cell 2005 17 595 601 15721262
  29. [33]Sauve AA Schramm VL Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistry Biochemistry 2003 42 9249 9256 12899610
  30. [34]Avalos JL Boeke JD Wolberger C Structural basis for the mechanism and regulation of Sir2 enzymes Mol. Cell 2004 13 639 648 15023335
  31. [35]Balan V Miller GS Kaplun L Balan K Chong ZZ Life span extension and neuronal cell protection by Drosophila nicotinamidase J. Biol. Chem 2008 283 27810 27819 18678867 PMC2562057
  32. [37]Gallo CM Smith DL Jr Smith JS Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity Mol. Cell Biol 2004 24 1301 1312 14729974 PMC321434
  33. [38]Bieganowski P Brenner C Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans Cell 2004 117 495 502 15137942
  34. [41]Rongvaux A Shea RJ Mulks MH Gigot D Urbain J Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis Eur. J. Immunol 2002 32 3225 3234 12555668
  35. [43]Yang H Lavu S Sinclair DA Nampt/PBEF/Visfatin: a regulator of mammalian health and longevity? Exp. Gerontol 2006 41 718 726 16842957 PMC3366689
  36. [44]Yang H Yang T Baur JA Perez E Matsui T Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival Cell 2007 130 1095 1107 17889652 PMC3366687
  37. [45]Zhang T Berrocal JG Frizzell KM Gamble MJ Dumond ME Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters J. Biol. Chem 2009 284 20408 20417 19478080 PMC2740465
  38. [47]Imai S The NAD world: a new systemic regulatory network for metabolism and aging—Sirt1, systemic NAD biosynthesis, and their importance Cell Biochem. Biophys 2009 53 65 74 19130305 PMC2734380
  39. [48]Bogan KL Brenner C Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition Annu. Rev. Nutr 2008 28 115 130 18429699
  40. [50]Rutter J Reick M Wu LC McKnight SL Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors Science 2001 293 510 514 11441146
  41. [51]Ramsey KM Yoshino J Brace CS Abrassart D Kobayashi Y Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis Science 2009 324 651 654 19299583 PMC2738420
  42. [52]Jung-Hynes B Ahmad N SIRT1 controls circadian clock circuitry and promotes cell survival: a connection with age-related neoplasms FASEB J 2009 23 2803 2809 19439501 PMC2796903
  43. [53]Nakahata Y Sahar S Astarita G Kaluzova M Sassone-Corsi P Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1 Science 2009 324 654 657 19286518 PMC6501775
  44. [54]Aksoy P Escande C White TA Thompson M Soares S Regulation of SIRT 1 mediated NAD dependent deacetylation: a novel role for the multifunctional enzyme CD38 Biochem. Biophys. Res. Commun 2006 349 353 359 16935261
  45. [55]Lund FE Signaling properties of CD38 in the mouse immune system: enzyme-dependent and -independent roles in immunity Mol. Med 2006 12 328 333 17380200 PMC1829203
  46. [56]Liou GG Tanny JC Kruger RG Walz T Moazed D Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation Cell 2005 121 515 527 15907466
  47. [57]Grubisha O Rafty LA Takanishi CL Xu X Tong L Metabolite of SIR2 reaction modulates TRPM2 ion channel J. Biol. Chem 2006 281 14057 14065 16565078
  48. [58]Rafty LA Schmidt MT Perraud AL Scharenberg AM Denu JM Analysis of O-acetyl-ADP-ribose as a target for nudix ADP-ribose hydrolases J. Biol. Chem 2002 277 47114 47122 12370179
  49. [59]Michan S Sinclair D Sirtuins in mammals: insights into their biological function Biochem. J 2007 404 1 13 17447894 PMC2753453
  50. [60]North BJ Verdin E Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis PLoS ONE 2007 2 e784 17726514 PMC1949146
  51. [61]Tanno M Sakamoto J Miura T Shimamoto K Horio Y Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1 J. Biol. Chem 2007 282 6823 6832 17197703
  52. [62]Cohen HY Lavu S Bitterman KJ Hekking B Imahiyerobo TA Acetylation of the C terminus of Ku70 by CBP and PCAF controls bax-mediated apoptosis Mol. Cell 2004 13 627 638 15023334
  53. [64]Schwer B North BJ Frye RA Ott M Verdin E The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase J. Cell Biol 2002 158 647 657 12186850 PMC2174009
  54. [65]Schwer B Bunkenborg J Verdin RO Andersen JS Verdin E Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2 Proc. Natl. Acad. Sci. USA 2006 103 10224 10229 16788062 PMC1502439
  55. [66]Hallows WC Albaugh BN Denu JM Where in the cell is SIRT3? Functional localization of an NAD+-dependent protein deacetylase Biochem. J 2008 411 e11 e13 18363549 PMC3313448
  56. [67]Nakamura Y Ogura M Tanaka D Inagaki N Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5 Biochem. Biophys. Res. Commun 2008 366 174 179 18054327
  57. [68]Scher MB Vaquero A Reinberg D SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress Genes Dev 2007 21 920 928 17437997 PMC1847710
  58. [69]Jin L Wei W Jiang Y Peng H Cai J Crystal structures of human SIRT3 displaying substrate-induced conformational changes J. Biol. Chem 2009 284 24394 24405 19535340 PMC2782032
  59. [70]Sinclair DA Toward a unified theory of caloric restriction and longevity regulation Mech. Ageing Dev 2005 126 987 1002 15893363
  60. [71]Harper JM Leathers CW Austad SN Does caloric restriction extend life in wild mice? Aging Cell 2006 5 441 449 17054664 PMC2923404
  61. [72]Cooper TM Mockett RJ Sohal BH Sohal RS Orr WC Effect of caloric restriction on life span of the housefly, Musca domestica FASEB J 2004 18 1591 1593 15319362
  62. [73]Guarente L Kenyon C Genetic pathways that regulate ageing in model organisms Nature 2000 408 255 262 11089983
  63. [74]Lin SJ Kaeberlein M Andalis AA Sturtz LA Defossez PA Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration Nature 2002 418 344 348 12124627
  64. [75]Lamming DW Latorre-Esteves M Medvedik O Wong SN Tsang FA HST2 mediates SIR2-independent life-span extension by calorie restriction Science 2005 309 1861 1864 16051752
  65. [76]Kaeberlein M Hu D Kerr EO Tsuchiya M Westman EA Increased life span due to calorie restriction in respiratory-deficient yeast PLoS Genet 2005 1 e69 16311627 PMC1287956
  66. [77]Kaeberlein M Kirkland KT Fields S Kennedy BK Sir2-independent life span extension by calorie restriction in yeast PLoS Biol 2004 2 E296 15328540 PMC514491
  67. [78]Fabrizio P Gattazzo C Battistella L Wei M Cheng C Sir2 blocks extreme life-span extension Cell 2005 123 655 667 16286010
  68. [79]Bishop NA Guarente L Two neurons mediate diet-restriction-induced longevity in C. elegans Nature 2007 447 545 549 17538612
  69. [81]Medvedik O Lamming DW Kim KD Sinclair DA MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae PLoS Biol 2007 5 e261 17914901 PMC1994990
  70. [82]Anderson RM Bitterman KJ Wood JG Medvedik O Cohen H Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels J. Biol. Chem 2002 277 18881 18890 11884393
  71. [83]Masoro EJ Caloric restriction and aging: an update Exp. Gerontol 2000 35 299 305 10832051
  72. [84]Rattan SI Aging, anti-aging, and hormesis Mech. Ageing Dev 2004 125 285 289 15063104
  73. [85]Sinclair DA Howitz KT Dietary Restriction, Hormesis, and Small Molecule Mimetics 2006 Amsterdam/Boston Elsevier 660
  74. [86]Qin W Yang T Ho L Zhao Z Wang J Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction J. Biol. Chem 2006 281 21745 21754 16751189
  75. [87]Canto C Gerhart-Hines Z Feige JN Lagouge M Noriega L AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity Nature 2009 458 1056 1060 19262508 PMC3616311
  76. [88]Cohen HY Miller C Bitterman KJ Wall NR Hekking B Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase Science 2004 305 390 392 15205477
  77. [89]Chen D Bruno J Easlon E Lin SJ Cheng HL Tissue-specific regulation of SIRT1 by calorie restriction Genes Dev 2008 22 1753 1757 18550784 PMC2492662
  78. [91]Bordone L Cohen D Robinson A Motta MC van Veen E SIRT1 transgenic mice show phenotypes resembling calorie restriction Aging Cell 2007 6 759 767 17877786
  79. [92]Banks AS Kon N Knight C Matsumoto M Gutierrez-Juarez R SirT1 gain of function increases energy efficiency and prevents diabetes in mice Cell Metab 2008 8 333 341 18840364 PMC3222897
  80. [93]Pfluger PT Herranz D Velasco-Miguel S Serrano M Tschop MH Sirt1 protects against high-fat diet-induced metabolic damage Proc. Natl. Acad. Sci. USA 2008 105 9793 9798 18599449 PMC2474520
  81. [95]Baur JA Pearson KJ Price NL Jamieson HA Lerin C Resveratrol improves health and survival of mice on a high-calorie diet Nature 2006 444 337 342 17086191 PMC4990206
  82. [98]Li Y Xu W McBurney MW Longo VD SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons Cell Metab 2008 8 38 48 18590691 PMC2822839
  83. [99]McBurney MW Yang X Jardine K Hixon M Boekelheide K The mammalian SIR2α protein has a role in embryogenesis and gametogenesis Mol. Cell Biol 2003 23 38 54 12482959 PMC140671
  84. [100]Wang C Chen L Hou X Li Z Kabra N Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage Nat. Cell Biol 2006 8 1025 1031 16892051
  85. [101]Nemoto S Fergusson MM Finkel T Nutrient availability regulates SIRT1 through a forkhead-dependent pathway Science 2004 306 2105 2108 15604409
  86. [102]Chen WY Wang DH Yen RC Luo J Gu W Baylin SB Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses Cell 2005 123 437 448 16269335
  87. [104]Rane S He M Sayed D Vashistha H Malhotra A Downregulation of miR-199a derepresses hypoxia-inducible factor-1α and sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes Circ. Res 2009 104 879 886 19265035 PMC3332328
  88. [105]Yamakuchi M Lowenstein CJ MiR-34, SIRT1 and p53: the feedback loop Cell Cycle 2009 8 712 715 19221490
  89. [106]Pogribny IP Muskhelishvili L Tryndyak VP Beland FA The tumor-promoting activity of 2-acetylaminofluorene is associated with disruption of the p53 signaling pathway and the balance between apoptosis and cell proliferation Toxicol. Appl. Pharmacol 2009 235 305 311 19167416
  90. [107]Fujita Y Kojima K Hamada N Ohhashi R Akao Y Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells Biochem. Biophys. Res. Commun 2008 377 114 119 18834855
  91. [108]Yamakuchi M Ferlito M Lowenstein CJ miR-34a repression of SIRT1 regulates apoptosis Proc. Natl. Acad. Sci. USA 2008 105 13421 13426 18755897 PMC2533205
  92. [109]Yuan J Minter-Dykhouse K Lou Z A c-Myc-SIRT1 feedback loop regulates cell growth and transformation J. Cell Biol 2009 185 203 211 19364925 PMC2700370
  93. [110]Solomon JM Pasupuleti R Xu L McDonagh T Curtis R Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage Mol. Cell Biol 2006 26 28 38 16354677 PMC1317617
  94. [111]Mai A Massa S Lavu S Pezzi R Simeoni S Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (sirtuin) inhibitors J. Med. Chem 2005 48 7789 7795 16302818
  95. [112]Smith JJ Kenney RD Gagne DJ Frushour BP Ladd W Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo BMC Syst. Biol 2009 3 31 19284563 PMC2660283
  96. [113]Howitz KT Bitterman KJ Cohen HY Lamming DW Lavu S Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan Nature 2003 425 191 196 12939617
  97. [114]Lavu S Boss O Elliott PJ Lambert PD Sirtuins—novel therapeutic targets to treat age-associated diseases Nat. Rev. Drug Discov 2008 7 841 853 18827827
  98. [115]Bauer JH Goupil S Garber GB Helfand SL An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster Proc. Natl. Acad. Sci. USA 2004 101 12980 12985 15328413 PMC516504
  99. [116]Wood JG Rogina B Lavu S Howitz K Helfand SL Sirtuin activators mimic caloric restriction and delay ageing in metazoans Nature 2004 430 686 689 15254550
  100. [117]Jarolim S Millen J Heeren G Laun P Goldfarb DS Breitenbach M A novel assay for replicative lifespan in Saccharomyces cerevisiae FEMS Yeast Res 2004 5 169 177 15489200
  101. [118]Viswanathan M Kim SK Berdichevsky A Guarente L A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span Dev. Cell 2005 9 605 615 16256736
  102. [119]Bass TM Weinkove D Houthoofd K Gems D Partridge L Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans Mech. Ageing Dev 2007 128 546 552 17875315
  103. [120]Kaeberlein M McDonagh T Heltweg B Hixon J Westman EA Substrate-specific activation of sirtuins by resveratrol J. Biol. Chem 2005 280 17038 17045 15684413
  104. [121]Nayagam VM Wang X Tan YC Poulsen A Goh KC SIRT1 modulating compounds from high-throughput screening as anti-inflammatory and insulin-sensitizing agents J. Biomol. Screen 2006 11 959 967 17099246
  105. [122]Galonek H Miller C Israelian K Ribish S Lynch AV Enzymatic and cellular activity of small molecule activators of SIRT1 2009 Presented at NAD Metab. Signal., FASEB J. Conf. Carefree, Ariz.
  106. [123]Wang RH Zheng Y Kim HS Xu X Cao L Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis Mol. Cell 2008 32 11 20 18851829 PMC2577018
  107. [124]Sun C Zhang F Ge X Yan T Chen X SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B Cell Metab 2007 6 307 319 17908559
  108. [125]Boily G He XH Pearce B Jardine K McBurney MW SirT1-null mice develop tumors at normal rates but are poorly protected by resveratrol Oncogene 2009 28 2882 2893 19503100
  109. [126]Kim EJ Kho JH Kang MR Um SJ Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity Mol. Cell 2007 28 277 290 17964266
  110. [127]Hasegawa K Yoshikawa K Necdin regulates p53 acetylation via Sirtuin1 to modulate DNA damage response in cortical neurons J. Neurosci 2008 28 8772 8784 18753379 PMC6670824
  111. [128]Zhao W Kruse JP Tang Y Jung SY Qin J Gu W Negative regulation of the deacetylase SIRT1 by DBC1 Nature 2008 451 587 590 18235502 PMC2866287
  112. [129]Kim JE Chen J Lou Z DBC1 is a negative regulator of SIRT1 Nature 2008 451 583 586 18235501
  113. [130]Sasaki T Maier B Koclega KD Chruszcz M Gluba W Phosphorylation regulates SIRT1 function PLoS One 2008 3 e4020 19107194 PMC2602979
  114. [131]Puigserver P Wu Z Park CW Graves R Wright M Spiegelman BM A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis Cell 1998 92 829 839 9529258
  115. [133]Rodgers JT Lerin C Gerhart-Hines Z Puigserver P Metabolic adaptations through the PGC-1α and SIRT1 pathways FEBS Lett 2008 582 46 53 18036349 PMC2275806
  116. [134]Purushotham A Schug TT Xu Q Surapureddi S Guo X Li X Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation Cell Metab 2009 9 327 328 19356714 PMC2668535
  117. [135]Liu Y Dentin R Chen D Hedrick S Ravnskjaer K A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange Nature 2008 456 269 273 18849969 PMC2597669
  118. [136]Canto C Auwerx J PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure Curr. Opin. Lipidol 2009 20 98 105 19276888 PMC3627054
  119. [137]Canto C Auwerx J Glucose restriction: longevity SIRTainly, but without building muscle? Dev. Cell 2008 14 642 644 18477447
  120. [139]Kim D Nguyen MD Dobbin MM Fischer A Sananbenesi F SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis EMBO J 2007 26 3169 3179 17581637 PMC1914106
  121. [140]Gerhart-Hines Z Rodgers JT Bare O Lerin C Kim SH Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1α EMBO J 2007 26 1913 1923 17347648 PMC1847661
  122. [141]Ajmo JM Liang X Rogers CQ Pennock B You M Resveratrol alleviates alcoholic fatty liver in mice Am. J. Physiol. Gastrointest. Liver Physiol 2008 295 G833 G842 18755807 PMC2575919
  123. [142]You M Liang X Ajmo JM Ness GC Involvement of mammalian sirtuin 1 in the action of ethanol in the liver Am. J. Physiol. Gastrointest. Liver Physiol 2008 294 G892 G898 18239056
  124. [143]Li X Zhang S Blander G Tse JG Krieger M Guarente L SIRT1 deacetylates and positively regulates the nuclear receptor LXR Mol. Cell 2007 28 91 106 17936707
  125. [144]Lee IH Cao L Mostoslavsky R Lombard DB Liu J A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy Proc. Natl. Acad. Sci. USA 2008 105 3374 3379 18296641 PMC2265142
  126. [145]Moynihan KA Grimm AA Plueger MM Bernal-Mizrachi E Ford E Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice Cell Metab 2005 2 105 117 16098828
  127. [146]Bordone L Motta MC Picard F Robinson A Jhala US Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic β cells PLoS Biol 2006 4 e31 16366736 PMC1318478
  128. [148]Picard F Kurtev M Chung N Topark-Ngarm A Senawong T Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ Nature 2004 429 771 776 15175761 PMC2820247
  129. [149]Qiao L Shao J SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein α transcriptional complex J. Biol. Chem 2006 281 39915 39924 17090532
  130. [150]Wallace DC A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine Annu. Rev. Genet 2005 39 359 407 16285865 PMC2821041
  131. [152]Onyango P Celic I McCaffery JM Boeke JD Feinberg AP SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria Proc. Natl. Acad. Sci. USA 2002 99 13653 13658 12374852 PMC129731
  132. [154]Lombard DB Alt FW Cheng HL Bunkenborg J Streeper RS Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation Mol. Cell Biol 2007 27 8807 8814 17923681 PMC2169418
  133. [155]Hallows WC Lee S Denu JM Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases Proc. Natl. Acad. Sci. USA 2006 103 10230 10235 16790548 PMC1480596
  134. [156]Schlicker C Gertz M Papatheodorou P Kachholz B Becker CF Steegborn C Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5 J. Mol. Biol 2008 382 790 801 18680753
  135. [157]Ahn BH Kim HS Song S Lee IH Liu J A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis Proc. Natl. Acad. Sci. USA 2008 105 14447 14452 18794531 PMC2567183
  136. [158]Jin L Galonek H Israelian K Choy W Morrison M Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3 Protein Sci 2009 18 514 525 19241369 PMC2760358
  137. [159]Bellizzi D Dato S Cavalcante P Covello G Di Cianni F Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13 Genomics 2007 89 143 150 17059877
  138. [161]Ahuja N Schwer B Carobbio S Waltregny D North BJ Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase J. Biol. Chem 2007 282 33583 33592 17715127
  139. [162]Stanley CA Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism Mol. Genet. Metab 2004 81 Suppl. 1 S45 S51 15050973
  140. [163]Sundaresan NR Samant SA Pillai VB Rajamohan SB Gupta MP SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70 Mol. Cell Biol 2008 28 6384 6401 18710944 PMC2577434
  141. [164]Palacios OM Carmona JJ Michan S Chen K Manabe Y Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1α in skeletal muscle Aging 2009 In press PMC2815736 20157566
  142. [165]Brooks CL Gu W p53 Activation: a case against Sir Cancer Cell 2008 13 377 378 18455119 PMC2856338
  143. [166]Brooks CL Gu W How does SIRT1 affect metabolism, senescence and cancer? Nat. Rev. Cancer 2009 9 123 128 19132007 PMC2857763
  144. [167]Luo J Nikolaev AY Imai S Chen D Su F Negative control of p53 by Sir2α promotes cell survival under stress Cell 2001 107 137 148 11672522
  145. [168]Vaziri H Dessain SK Eaton EN Imai SI Frye RA hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase Cell 2001 107 149 159 11672523
  146. [169]Firestein R Blander G Michan S Oberdoerffer P Ogino S The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth PLoS ONE 2008 3 e2020 18414679 PMC2289879
  147. [170]Oberdoerffer P Michan S McVay M Mostoslavsky R Vann J SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging Cell 2008 135 907 918 19041753 PMC2853975
  148. [171]Deng CX SIRT1, is it a tumor promoter or tumor suppressor? Int. J. Biol. Sci 2009 5 147 152 19173036 PMC2631220
  149. [173]Zhang Y Zhang M Dong H Yong S Li X Deacetylation of cortactin by SIRT1 promotes cell migration Oncogene 2009 28 445 460 18850005
  150. [174]Huffman DM Grizzle WE Bamman MM Kim JS Eltoum IA SIRT1 is significantly elevated in mouse and human prostate cancer Cancer Res 2007 67 6612 6618 17638871
  151. [175]Bradbury CA Khanim FL Hayden R Bunce CM White DA Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors Leukemia 2005 19 1751 1759 16121216
  152. [176]Stunkel W Peh BK Tan YC Nayagam VM Wang X Function of the SIRT1 protein deacetylase in cancer Biotechnol. J 2007 2 1360 1368 17806102
  153. [177]Hida Y Kubo Y Murao K Arase S Strong expression of a longevity-related protein, SIRT1, in Bowen’s disease Arch. Dermatol. Res 2007 299 103 106 17180656
  154. [178]Wang RH Sengupta K Li C Kim HS Cao L Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice Cancer Cell 2008 14 312 323 18835033 PMC2643030
  155. [179]Ouaissi M Sielezneff I Silvestre R Sastre B Bernard JP High histone deacetylase 7 (HDAC7) expression is significantly associated with adenocarcinomas of the pancreas Ann. Surg. Oncol 2008 15 2318 2328 18506539
  156. [180]North BJ Verdin E Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent phosphorylation J. Biol. Chem 2007 282 19546 19555 17488717
  157. [181]Inoue T Nakayama Y Yamada H Li YC Yamaguchi S SIRT2 downregulation confers resistance to microtubule inhibitors by prolonging chronic mitotic arrest Cell Cycle 2009 8 1279 1291 19282667
  158. [182]Hiratsuka M Inoue T Toda T Kimura N Shirayoshi Y Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene Biochem. Biophys. Res. Commun 2003 309 558 566 12963026
  159. [183]Das C Lucia MS Hansen KC Tyler JK CBP/p300-mediated acetylation of histone H3 on lysine 56 Nature 2009 459 113 117 19270680 PMC2756583
  160. [184]Inoue T Hiratsuka M Osaki M Yamada H Kishimoto I SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress Oncogene 2007 26 945 957 16909107
  161. [185]Ashraf N Zino S Macintyre A Kingsmore D Payne AP Altered sirtuin expression is associated with node-positive breast cancer Br. J. Cancer 2006 95 1056 1061 17003781 PMC2360714
  162. [186]Frye R “SIRT8” expressed in thyroid cancer is actually SIRT7 Br. J. Cancer 2002 87 1479 12454781 PMC2376300
  163. [188]Ford J Jiang M Milner J Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival Cancer Res 2005 65 10457 10463 16288037
  164. [189]Lara E Mai A Calvanese V Altucci L Lopez-Nieva P Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect Oncogene 2009 28 781 791 19060927
  165. [190]Luo J Nikolaev AY Imai S Chen D Su F Negative control of p53 by Sir2α promotes cell survival under stress Cell 2001 107 137 148 11672522
  166. [191]Lain S Hollick JJ Campbell J Staples OD Higgins M Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator Cancer Cell 2008 13 454 463 18455128 PMC2742717
  167. [192]Cheng HL Mostoslavsky R Saito S Manis JP Gu Y Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice Proc. Natl. Acad. Sci. USA 2003 100 10794 10799 12960381 PMC196882
  168. [193]Ota H Tokunaga E Chang K Hikasa M Iijima K Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells Oncogene 2006 25 176 185 16170353
  169. [194]Ota H Akishita M Eto M Iijima K Kaneki M Ouchi Y Sirt1 modulates premature senescence-like phenotype in human endothelial cells J. Mol. Cell Cardiol 2007 43 571 579 17916362
  170. [195]Huang J Gan Q Han L Li J Zhang H SIRT1 overexpression antagonizes cellular senescence with activated ERK/S6k1 signaling in human diploid fibroblasts PLoS ONE 2008 3 e1710 18320031 PMC2249701
  171. [196]Vijg J Maslov AY Suh Y Aging: a sirtuin shake-up? Cell 2008 135 797 798 19041745
  172. [197]Potente M Ghaeni L Baldessari D Mostoslavsky R Rossig L SIRT1 controls endothelial angiogenic functions during vascular growth Genes Dev 2007 21 2644 2658 17938244 PMC2000327
  173. [198]Potente M Dimmeler S Emerging roles of SIRT1 in vascular endothelial homeostasis Cell Cycle 2008 7 2117 2122 18641460
  174. [200]Yuan Z Seto E A functional link between SIRT1 deacetylase and NBS1 in DNA damage response Cell Cycle 2007 6 2869 2871 18156798
  175. [201]Anantharaman V Aravind L Analysis of DBC1 and its homologs suggests a potential mechanism for regulation of sirtuin domain deacetylases by NAD metabolites Cell Cycle 2008 7 1467 1472 18418069 PMC2423810
  176. [202]Yeung F Hoberg JE Ramsey CS Keller MD Jones DR Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase EMBO J 2004 23 2369 2380 15152190 PMC423286
  177. [203]Masoro EJ Retardation of aging processes by food restriction: an experimental tool Am. J. Clin. Nutr 1992 55 1250S 1252S 1590266
  178. [205]Baur JA Sinclair DA Therapeutic potential of resveratrol: the in vivo evidence Nat. Rev. Drug Discov 2006 5 493 506 16732220
  179. [206]Jacks T Remington L Williams BO Schmitt EM Halachmi S Tumor spectrum analysis in p53-mutant mice Curr. Biol 1994 4 1 7 7922305
  180. [207]Kemp CJ Wheldon T Balmain A p53-deficient mice are extremely susceptible to radiation-induced tumorigenesis Nat. Genet 1994 8 66 69 7987394
  181. [208]Donehower LA Harvey M Slagle BL McArthur MJ Montgomery CA Jr Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours Nature 1992 356 215 221 1552940
  182. [209]Imai S Kitano H Heterochromatin islands and their dynamic reorganization: a hypothesis for three distinctive features of cellular aging Exp. Gerontol 1998 33 555 570 9789733
  183. [210]Kamel C Abrol M Jardine K He X McBurney MW Sirt1 fails to affect p53-mediated biological functions Aging Cell 2006 5 81 88 16441846
  184. [213]Martin SG Laroche T Suka N Grunstein M Gasser SM Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast Cell 1999 97 621 633 10367891
  185. [214]Lee SE Paques F Sylvan J Haber JE Role of yeast SIR genes and mating type in directing DNA double-strand breaks to homologous and non-homologous repair paths Curr. Biol 1999 9 767 770 10421582
  186. [215]Bennett CB Snipe JR Westmoreland JW Resnick MA SIR functions are required for the toleration of an unrepaired double-strand break in a dispensable yeast chromosome Mol. Cell Biol 2001 21 5359 5373 11463819 PMC87259
  187. [216]Tamburini BA Tyler JK Localized histone acetylation and deacetylation triggered by the homologous recombination pathway of double-strand DNA repair Mol. Cell Biol 2005 25 4903 4913 15923609 PMC1140608
  188. [217]Yuan Z Zhang X Sengupta N Lane WS Seto E SIRT1 regulates the function of the Nijmegen breakage syndrome protein Mol. Cell 2007 27 149 162 17612497 PMC2679807
  189. [218]Jang M Cai L Udeani GO Slowing KV Thomas CF Cancer chemopreventive activity of resveratrol, a natural product derived from grapes Science 1997 175 218 220 8985016
  190. [220]Dryden SC Nahhas FA Nowak JE Goustin AS Tainsky MA Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle Mol. Cell Biol 2003 23 3173 3185 12697818 PMC153197
  191. [221]Zhang Y Au Q Zhang M Barber JR Ng SC Zhang B Identification of a small-molecule SIRT2 inhibitor with selective tumor cytotoxicity Biochem. Biophys. Res. Commun 2009 386 729 733 19559674
  192. [222]Heltweg B Gatbonton T Schuler AD Posakony J Li H Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes Cancer Res 2006 66 4368 4377 16618762
  193. [223]Allison SJ Milner J SIRT3 is pro-apoptotic and participates in distinct basal apoptotic pathways Cell Cycle 2007 6 2669 2677 17957139
  194. [224]Mostoslavsky R Chua KF Lombard DB Pang WW Fischer MR Genomic instability and aging-like phenotype in the absence of mammalian SIRT6 Cell 2006 124 315 329 16439206
  195. [225]Ma W Stafford LJ Li D Luo J Li X GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis J. Cell Biochem 2007 100 1376 1386 17131381
  196. [226]Matoba S Kang JG Patino WD Wragg A Boehm M p53 regulates mitochondrial respiration Science 2006 312 1650 1653 16728594
  197. [227]Bakhanashvili M Grinberg S Bonda E Simon AJ Moshitch-Moshkovitz S Rahav G p53 in mitochondria enhances the accuracy of DNA synthesis Cell Death Differ 2008 15 1865 1874 19011642
  198. [228]Malik S Wong ND Franklin SS Kamath TV L’Italien GJ Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults Circulation 2004 110 1245 1250 15326067
  199. [229]Heilbronn LK de Jonge L Frisard MI DeLany JP Larson-Meyer DE Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial JAMA 2006 295 1539 1548 16595757 PMC2692623
  200. [231]Bitterman KJ Medvedik O Sinclair DA Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin Microbiol. Mol. Biol. Rev 2003 67 376 399 12966141 PMC193872

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Authors
Haigis, M. C., & Sinclair, D. A.
Affiliations
Harvard University (US)
ORCID
Venue
Annual Review of Pathology: Mechanisms of Disease
Publisher
Annual Reviews
Published
2010-01-01
Volume
5
Issue
1
Pages
253-295
ISSN
  • 1553-4006 (ISSN-L)
  • 1553-4014
DOI
10.1146/annurev.pathol.4.110807.092250
PMC
PMC2866163
OpenAlex
W2118964113
Cited by
2,085
References
36
Citations by year
2026: 78 · 2025: 118 · 2024: 80 · 2023: 113 · 2022: 123 · 2021: 152 · 2020: 143 · 2019: 124 · 2018: 148 · 2017: 115 · 2016: 142 · 2015: 117 · 2014: 154 · 2013: 145 · 2012: 149
FWCI
13.23
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Pathology Mechanisms of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (R01AG032375, P01AG027916, R01AG028730, R01AG019719)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
sirtuins, SIRT1, aging, healthspan, longevity, type 2 diabetes, neurodegenerative diseases, cancer, cardiovascular disease
MeSH terms
Aging, Animals, Cardiovascular Diseases, Humans, Longevity, Metabolic Diseases, Neoplasms, Neurodegenerative Diseases, Sirtuins

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