The role of sirtuins in aging and age-related diseases

Advances in Medical Sciences

Volumn 61, Issue 1, 2016, Pages 52-62

  Wa¸troba, Mateusz ^a   Szukiewicz, Dariusz ^a  

^a MEDICAL UNIVERSITY OF WARSAW   (Poland)

Author keywords

Aging; Carcinogenesis; Healthspan; Lifespan regulation; Metabolic syndrome

Indexed keywords

ADENOSINE TRIPHOSPHATE; ATM PROTEIN; ATR PROTEIN; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 45; HISTONE H3; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MYC PROTEIN; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; NUCLEAR RESPIRATORY FACTOR 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PROTEIN C JUN; PROTEIN P53; PROTEINASE ACTIVATED RECEPTOR 3; SIRTUIN; SIRTUIN 1; SIRTUIN 2; SIRTUIN 3; SIRTUIN 4; SIRTUIN 5; SIRTUIN 6; SIRTUIN 7; TRANSCRIPTION FACTOR FOXO;

AGING; ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; ATHEROGENESIS; CALORIC RESTRICTION; CANCER CELL LINE; CARCINOGENESIS; CELL CYCLE; CELL FUNCTION; CELL METABOLISM; CELL RESPIRATION; CITRIC ACID CYCLE; DEACETYLATION; DEACYLATION; DNA DAMAGE; DNA REPAIR; ENERGY CONSUMPTION; GENE OVEREXPRESSION; GENE SILENCING; GENOMIC INSTABILITY; GERIATRIC DISORDER; GLUCONEOGENESIS; GLYCOLYSIS; HEART VENTRICLE HYPERTROPHY; HOMOLOGOUS RECOMBINATION; HUMAN; HYPERGLYCEMIA; INFLAMMATION; INTRACELLULAR SIGNALING; LIPOLYSIS; LONGEVITY; METABOLIC DISORDER; MITOCHONDRIAL BIOGENESIS; MITOCHONDRIAL FUNCTION; MITOCHONDRION; NERVE FIBER GROWTH; NEUROPROTECTION; NONHUMAN; NUTRIENT AVAILABILITY; OXIDATION REDUCTION STATE; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PREMATURE AGING; PROMOTER REGION; REVIEW; UPREGULATION; WERNER SYNDROME; WHITE ADIPOSE TISSUE; ANIMAL; BIOLOGICAL MODEL; DISEASES; METABOLISM;

AGING; ANIMALS; DISEASE; HUMANS; MODELS, BIOLOGICAL; NAD; SIRTUINS;

EID: 84960153337     PISSN: 18961126     EISSN: 18984002     Source Type: Journal    
DOI: 10.1016/j.advms.2015.09.003     Document Type: Review

References (176)

1. S.S. Mahajan, L. Vid, J.A. Simon, and A. Bedalov Sirtuin modulators Handb Exp Pharmacol 206 2011 241 255
2. L. Guarente Sir2 links chromatin silencing, metabolism, and aging Genes Dev 14 9 2000 1021 1026
3. R.K. Mortimer, and J.R. Johnston Life span of individual yeast cells Nature 183 4677 1959 1751 1752
4. D.A. Sinclair, and L. Guarente Extrachromosomal rDNA circles - a cause of aging in yeast Cell 91 7 1997 1033 1042
5. H.A. Tissenbaum, and L. Guarente Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans Nature 410 6825 2001 227 230
6. B. Rogina, and S.L. Helfand Sir2 mediates longevity in the fly through a pathway related to calorie restriction Proc Natl Acad Sci U S A 101 45 2004 15998 16003
7. L. Bordone, and L. Guarente Calorie restriction, SIRT1 and metabolism: understanding longevity Nat Rev Mol Cell Biol 6 4 2005 298 305
8. S. Carlos, F.K. Satterstrom, M. Haigis, and R. Mostoslavsky From sirtuin biology to human diseases: an update J Biol Chem 287 51 2012 42444 42452
9. D. Wu, Y. Qiu, X. Gao, X.B. Yuan, and Q. Zhai Overexpression of SIRT1 in mouse forebrain impairs lipid/glucose metabolism and motor function PLoS ONE 6 6 2011 e21759
10. Y. Kanfi, R. Shalman, V. Peshti, S.N. Pilosof, Y.M. Gozlan, K.J. Pearson, and et al. Regulation of SIRT6 protein levels by nutrient availability FEBS Lett 582 5 2008 543 548
11. N.R. Sundaresan, P. Vasudevan, L. Zhong, G. Kim, S. Samant, V. Parekh, and et al. The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun Nat Med 18 11 2012 1643 1650
12. A. Dávalos, L. Goedeke, P. Smibert, C.M. Ramirez, N.P. Warrier, U. Andreo, and et al. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling Proc Natl Acad Sci U S A 108 2011 9232 9237
13. D. Bellizzi, G. Rose, P. Cavalcante, G. Covello, S. Dato, F. De Rango, and et al. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages Genomics 85 2005 258 263
14. F. Lescai, H. Blanche, A. Nebel, M. Beekman, M. Sahbatou, F. Flachsbart, and et al. Human longevity and 11p15.5: a study in 1321 centenarians Eur J Hum Genet 17 11 2009 1515 1519
15. R.R. Alcendor, S. Gao, P. Zhai, D. Zablocki, E. Holle, X. Yu, and et al. Sirt1 regulates aging and resistance to oxidative stress in the heart Circ Res 100 10 2007 1512 1521
16. J. Yu, S. Sadhukhan, L.G. Noriega, N. Moullan, B. He, R.S. Weiss, and et al. Metabolic characterization of a SIRT5 deficient mouse model Sci Rep 3 2013 2806
17. M. Kaeberlein, K.T. Kirkland, S. Fields, and B.K. Kennedy Sir2-independent life span extension by calorie restriction in yeast PLoS Biol 2 9 2004 E296
18. S.J. Lin, P.A. Defossez, and L. Guarente Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae Science 289 2000 2126 2128
19. S. Imai, and L. Guarente Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases Trends Pharmacol Sci 31 5 2010 212 220
20. + and sirtuins in aging and disease Trends Cell Biol 24 8 2014 464 471
21. K.G. Tanner, J. Landry, R. Sternglanz, and J.M. Denu Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product-1-O-acetyl-ADP-ribose Proc Natl Acad Sci U S A 97 26 2000 14178 14182
22. E.J. Kim, J.H. Kho, M.R. Kang, and S.J. Um Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity Mol Cell 28 2 2007 277 290
23. W. Zhao, J.P. Kruse, Y. Tang, S.Y. Jung, J. Qin, and W. Gu Negative regulation of the deacetylase SIRT1 by DBC1 Nature 451 7178 2008 587 590
24. + precursor vitamins in human nutrition Annu Rev Nutr 28 2008 115 130
25. A. Bedalov, M. Hirao, J. Posakony, M. Nelson, and J.A. Simon NAD-dependent deacetylase Hst1p controls biosynthesis and cellular NAD levels in Saccharomyces cerevisiae Mol Cell Biol 23 19 2003 7044 7054
26. + biosynthesis Science 324 5927 2009 651 654
27. + salvage pathway by CLOCK-SIRT1 Science 324 5927 2009 654 657
28. H.C. Ha, and S.H. Snyder Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion Proc Natl Acad Sci U S A 96 24 1999 13978 13982
29. + levels J Biol Chem 277 21 2002 18881 18890
30. R.M. Anderson, K.J. Bitterman, J.G. Wood, O. Medvedik, and D.A. Sinclair Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae Nature 423 6936 2003 181 185
31. J.R. Revollo, A.A. Grimm, and S. Imai The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells J Biol Chem 279 49 2004 50754 50763
32. S.J. Lin, E. Ford, M. Haigis, G. Liszt, and L. Guarente Calorie restriction extends yeast life span by lowering the level of NADH Genes Dev 18 1 2004 12 16
33. M. Fulco, R.L. Schiltz, S. Iezzi, M.T. King, P. Zhao, Y. Kashiwaya, and et al. Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state Mol Cell 12 2003 51 62
34. T. Prozorovski, U. Schulze-Topphoff, R. Glumm, J. Baumgart, F. Schröter, O. Ninnemann, and et al. Sirt1 contributes critically to the redox-dependent fate of neural progenitors Nat Cell Biol 10 4 2008 385 394
35. M.T. Schmidt, B.C. Smith, M.D. Jackson, and J.M. Denu Coenzyme specificity of Sir2 protein deacetylases: implications for physiological regulation J Biol Chem 279 38 2004 40122 40129
36. Q. Zhang, S.Y. Wang, C. Fleuriel, D. Leprince, J.V. Rocheleau, D.W. Piston, and et al. Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex Proc Natl Acad Sci U S A 104 3 2007 829 833
37. J.T. Rodgers, C. Lerin, W. Haas, S.P. Gygi, B.M. Spiegelman, and P. Puigserver Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1 Nature 434 7029 2005 113 118
38. J. Landry, A. Sutton, S.T. Tafrov, R.C. Heller, J. Stebbins, L. Pillus, and et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases Proc Natl Acad Sci U S A 97 11 2000 5807 5811
39. D.W.H. Brittain, and E. Ottow Recent advances in the medicinal chemistry of histone deacetylase inhibitors Ann Rep Med Chem 42 2007 337 348
40. S. Michan, and D. Sinclair Sirtuins in mammals: insights into their biological function Biochem J 404 1 2007 1 13
41. J.M. Villalba, and F.J. Alcain Sirtuin activators and inhibitors Biofactors 38 5 2012 349 359
42. H. Vaziri, S.K. Dessain, E. Ng Eaton, S.I. Imai, R.A. Frye, T.K. Pandita, and et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase Cell 107 2 2001 149 159
43. +-dependent tubulin deacetylase Mol Cell 11 2 2003 437 444
44. B.J. North, and E. Verdin Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis PLoS ONE 2 8 2007 e784
45. +-dependent histone deacetylase SIRT1 J Biol Chem 282 9 2007 6823 6832
46. E. Ford, R. Voit, G. Liszt, C. Magin, I. Grummt, and L. Guarente Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription Genes Dev 20 9 2006 1075 1080
47. U. Mahlknecht, A.D. Ho, and S. Voelter-Mahlknecht Chromosomal organization and fluorescence in situ hybridization of the human Sirtuin 6 gene Int J Oncol 28 2 2006 447 456
48. H.Y. Cohen, C. Miller, K.J. Bitterman, N.R. Wall, B. Hekking, B. Kessler, and et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase Science 305 5682 2004 390 392
49. J.P. Silva, and C. Wahlestedt Role of Sirtuin 1 in metabolic regulation Drug Discov Today 15 17-18 2010 781 791
50. S. Nemoto, M.M. Fergusson, and T. Finkel SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1alpha J Biol Chem 280 16 2005 16456 16460
51. G. Ramadori, C.E. Lee, A.L. Bookout, S. Lee, K.W. Williams, J. Anderson, and et al. Brain SIRT1: anatomical distribution and regulation by energy availability J Neurosci 28 40 2008 9989 9996
52. G. Ramadori, T. Fujikawa, M. Fukuda, J. Anderson, D.A. Morgan, R. Mostoslavsky, and et al. SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity Cell Metab 12 1 2010 78 87
53. S.J. Clark, M. Falchi, B. Olsson, P. Jacobson, S. Cauchi, B. Balkau, and et al. Association of sirtuin 1 (SIRT1) gene SNPs and transcript expression levels with severe obesity Obesity (Silver Spring) 20 1 2012 178 185
54. F. Flachsbart, P.J. Croucher, S. Nikolaus, J. Hampe, C. Cordes, S. Schreiber, and et al. Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity Exp Gerontol 41 1 2006 98 102
55. P. Chakrabarti, T. English, S. Karki, L. Qiang, R. Tao, J. Kim, and et al. SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL J Lipid Res 52 9 2011 1693 1701
56. B. Ponugoti, D.H. Kim, Z. Xiao, Z. Smith, J. Miao, M. Zang, and et al. SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism J Biol Chem 285 44 2010 33959 33970
57. A.K. Walker, F. Yang, K. Jiang, J.Y. Ji, J.L. Watts, A. Purushotham, and et al. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP Genes Dev 24 13 2010 1403 1417
58. A. Purushotham, Q. Xu, and X. Li Systemic SIRT1 insufficiency results in disruption of energy homeostasis and steroid hormone metabolism upon high-fat-diet feeding FASEB J 26 2 2012 656 667
59. P.T. Pfluger, D. Herranz, S. Velasco-Miguel, M. Serrano, and M.H. Tschöp Sirt1 protects against high-fat diet-induced metabolic damage Proc Natl Acad Sci U S A 105 28 2008 9793 9798
60. L. Qiang, H.V. Lin, J.Y. Kim-Muller, C.L. Welch, W. Gu, and D. Accili Proatherogenic abnormalities of lipid metabolism in SirT1 transgenic mice are mediated through Creb deacetylation Cell Metab 14 6 2011 758 767
61. H.S. Kim, C. Xiao, R.H. Wang, T. Lahusen, X. Xu, A. Vassilopoulos, and et al. Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis Cell Metab 12 3 2010 224 236
62. R.H. Houtkooper, E. Pirinen, and J. Auwerx Sirtuins as regulators of metabolism and healthspan Nat Rev Mol Cell Biol 13 4 2012 225 238
63. B. Martinez-Pastor, and R. Mostoslavsky Sirtuins, metabolism, and cancer Front Pharmacol 3 2012 22
64. J. Yuan, K. Minter-Dykhouse, and Z. Lou A c-Myc-SIRT1 feedback loop regulates cell growth and transformation J Cell Biol 185 2 2009 203 211
65. D. Herranz, M. Muñoz-Martin, M. Cañamero, F. Mulero, B. Martinez-Pastor, O. Fernandez-Capetillo, and et al. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer Nat Commun 1 2010 3
66. J.H. Lim, Y.M. Lee, Y.S. Chun, J. Chen, J.E. Kim, and J.W. Park Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1α Mol Cell 38 2010 864 878
67. C. Das, M.S. Lucia, K.C. Hansen, and J.K. Tyler CBP/p300-mediated acetylation of histone H3 on lysine 56 Nature 459 7243 2009 113 117
68. S. Elangovan, S. Ramachandran, N. Venkatesan, S. Ananth, J.P. Gnana-Prakasam, P.M. Martin, and et al. SIRT1 is essential for oncogenic signaling by estrogen/estrogen receptor α in breast cancer Cancer Res 71 21 2011 6654 6664
69. J. Chen, B. Zhang, N. Wong, A.W. Lo, K.F. To, A.W. Chan, and et al. Sirtuin 1 is upregulated in a subset of hepatocellular carcinomas where it is essential for telomere maintenance and tumor cell growth Cancer Res 71 12 2011 4138 4149
70. H.N. Choi, J.S. Bae, U. Jamiyandorj, S.J. Noh, H.S. Park, K.Y. Jang, and et al. Expression and role of SIRT1 in hepatocellular carcinoma Oncol Rep 26 2011 503 510
71. M.P. Gillum, M.E. Kotas, D.M. Erion, R. Kursawe, P. Chatterjee, K.T. Nead, and et al. SirT1 regulates adipose tissue inflammation Diabetes 60 12 2011 3235 3245
72. T.T. Schug, Q. Xu, H. Gao, A. Peres-da-Silva, D.W. Draper, M.B. Fessler, and et al. Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress Mol Cell Biol 30 19 2010 4712 4721
73. T. Yoshizaki, S. Schenk, T. Imamura, J.L. Babendure, N. Sonoda, E.J. Bae, and et al. SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity Am J Physiol Endocrinol Metab 298 3 2010 E419 E428
74. A. Planavila, R. Iglesias, M. Giralt, and F. Villarroya Sirt1 acts in association with PPARα to protect the heart from hypertrophy, metabolic dysregulation, and inflammation Cardiovasc Res 90 2 2011 276 284
75. S. Zhou, H.Z. Chen, Y.Z. Wan, Q.J. Zhang, Y.S. Wei, S. Huang, and et al. Repression of P66Shc expression by SIRT1 contributes to the prevention of hyperglycemia-induced endothelial dysfunction Circ Res 109 6 2011 639 648
76. F. Cosentino, P. Francia, G.G. Camici, P.G. Pelicci, T.F. Lüscher, and M. Volpe Final common molecular pathways of aging and cardiovascular disease: role of the p66Shc protein Arterioscler Thromb Vasc Biol 28 4 2008 622 628
77. G. Donmez, D. Wang, D.E. Cohen, and L. Guarente SIRT1 suppresses β-amyloid production by activating the α-secretase gene ADAM10 Cell 142 2 2010 320 332
78. S.W. Min, S.H. Cho, Y. Zhou, S. Schroeder, V. Haroutunian, W.W. Seeley, and et al. Acetylation of tau inhibits its degradation and contributes to tauopathy Neuron 67 6 2010 953 966
79. G. Donmez, A. Arun, C.Y. Chung, P.J. McLean, S. Lindquist, and L. Guarente SIRT1 protects against α-synuclein aggregation by activating molecular chaperones J Neurosci 32 1 2012 124 132
80. M. Jiang, J. Wang, J. Fu, L. Du, H. Jeong, T. West, and et al. Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets Nat Med 18 1 2011 153 158
81. H. Jeong, D.E. Cohen, L. Cui, A. Supinski, J.N. Savas, J.R. Mazzulli, and et al. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway Nat Med 18 1 2011 159 165
82. S. Michán, Y. Li, M.M. Chou, E. Parrella, H. Ge, J.M. Long, and et al. SIRT1 is essential for normal cognitive function and synaptic plasticity J Neurosci 30 29 2010 9695 9707
83. W. Guo, L. Qian, J. Zhang, W. Zhang, A. Morrison, P. Hayes, and et al. Sirt1 overexpression in neurons promotes neurite outgrowth and cell survival through inhibition of the mTOR signaling J Neurosci Res 89 11 2011 1723 1736
84. N. Kabra, Z. Li, L. Chen, B. Li, X. Zhang, C. Wang, and et al. SirT1 is an inhibitor of proliferation and tumor formation in colon cancer J Biol Chem 284 27 2009 18210 18217
85. F.J. Alcain, and J.M. Villalba Sirtuin inhibitors Expert Opin Ther Pat 19 3 2009 283 294
86. V. Audrito, T. Vaisitti, D. Rossi, D. Gottardi, G. D'Arena, L. Laurenti, and et al. Nicotinamide blocks proliferation and induces apoptosis of chronic lymphocytic leukemia cells through activation of the p53/miR-34a/SIRT1 tumor suppressor network Cancer Res 71 13 2011 4473 4483
87. R.H. Wang, K. Sengupta, C. Li, H.S. Kim, L. Cao, C. Xiao, and et al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice Cancer Cell 14 4 2008 312 323
88. W. Li, B. Zhang, J. Tang, Q. Cao, Y. Wu, C. Wu, and et al. Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating alpha-tubulin J Neurosci 27 10 2007 2606 2616
89. S.C. Dryden, F.A. Nahhas, J.E. Nowak, A.S. Goustin, and M.A. Tainsky Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle Mol Cell Biol 23 9 2003 3173 3185
90. M. Hiratsuka, T. Inoue, T. Toda, N. Kimura, Y. Shirayoshi, H. Kamitani, and et al. Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene Biochem Biophys Res Commun 309 3 2003 558 566
91. A. Erol Systemic DNA-damage response as and metabolic syndrome as a premalignant state Curr Mol Med 10 3 2010 321 334
92. P. Martinez-Redondo, and A. Vaquero The diversity of histone versus nonhistone sirtuin substrates Genes Cancer 4 3-4 2013 148 163
93. + system Genes Dev 26 3 2012 259 270
94. W. Jiang, S. Wang, M. Xiao, Y. Lin, L. Zhou, Q. Lei, and et al. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase Mol Cell 43 1 2011 33 44
95. E. Jing, S. Gesta, and C.R. Kahn SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation Cell Metab 6 2 2007 105 114
96. F. Wang, and Q. Tong SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARγ Mol Biol Cell 20 3 2009 801 808
97. H.S. Kim, A. Vassilopoulos, R.H. Wang, T. Lahusen, Z. Xiao, X. Xu, and et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity Cancer Cell 20 4 2011 487 499
98. K.M. Rothgiesser, S. Erener, S. Waibel, B. Lüscher, and M.O. Hottiger SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310 J Cell Sci 123 Pt 24 2010 4251 4258
99. S. Ji, J.R. Doucette, and A.J. Nazarali Sirt2 is a novel in vivo downstream target of Nkx2.2 and enhances oligodendroglial cell differentiation J Mol Cell Biol 3 6 2011 351 359
100. B. Beirowski, J. Gustin, S.M. Armour, H. Yamamoto, A. Viader, B.J. North, and et al. Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling Proc Natl Acad Sci U S A 108 43 2011 E952 E961
101. R. Luthi-Carter, D.M. Taylor, J. Pallos, E. Lambert, A. Amore, A. Parker, and et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis Proc Natl Acad Sci U S A 107 17 2010 7927 7932
102. E. Verdin, M.D. Hirschey, L.W. Finley, and M.C. Haigis Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling Trends Biochem Sci 35 12 2010 669 675
103. L.W. Finley, and M.C. Haigis Metabolic regulation by SIRT3: implications for tumorigenesis Trends Mol Med 18 9 2012 516 523
104. M.C. Haigis, C.X. Deng, L.W.S. Finley, H.S. Kim, and D. Gius SIRT3 is a mitochondrial tumor suppressor: a scientific tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis Cancer Res 72 10 2012 2468 2472
105. J.Y. Huang, M.D. Hirschey, T. Shimazu, L. Ho, and E. Verdin Mitochondrial sirtuins Biochim Biophys Acta 1804 8 2010 1645 1651
106. R. Tao, M.C. Coleman, J.D. Pennington, O. Ozden, S.H. Park, H. Jiang, and et al. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress Mol Cell 40 6 2010 893 904
107. X. Qiu, K. Brown, M.D. Hirschey, E. Verdin, and D. Chen Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation Cell Metabol 12 6 2010 662 667
108. L.W. Finley, A. Carracedo, J. Lee, A. Souza, A. Egia, J. Zhang, and et al. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization Cancer Cell 19 3 2011 416 428
109. E.L. Bell, B.M. Emerling, S.J. Ricoult, and L. Guarente SirT3 suppresses hypoxia inducible factor 1alpha and tumor growth by inhibiting mitochondrial ROS production Oncogene 30 26 2011 2986 2996
110. O. Warburg On the origin of cancer cells Science 123 3191 1956 309 331
111. H.S. Kim, K. Patel, K. Muldoon-Jacobs, K.S. Bisht, N. Aykin-Burns, J.D. Pennington, and et al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress Cancer Cell 17 1 2010 41 52
112. S. Li, M. Banck, S. Mujtaba, M.M. Zhou, M.M. Sugrue, and M.J. Walsh p53-induced growth arrest is regulated by the mitochondrial SirT3 deacetylase PLoS ONE 5 5 2010 e10486
113. J. Aury-Landas, G. Bougeard, H. Castel, H. Hernandez-Vargas, A. Drouet, J.B. Latouche, and et al. Germline copy number variation of genes involved in chromatin remodelling in families suggestive of Li-Fraumeni syndrome with brain tumours Eur J Hum Genet 21 12 2013 1369 1376
114. N. Ashraf, S. Zino, A. Macintyre, D. Kingsmore, A.P. Payne, W.D. George, and et al. Altered sirtuin expression is associated with node-positive breast cancer Br J Cancer 95 8 2006 1056 1061
115. G. Rose, S. Dato, K. Altomare, D. Bellizzi, S. Garasto, V. Greco, and et al. Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly Exp Gerontol 38 10 2003 1065 1070
116. W. Giblin, M.E. Skinner, and D.B. Lombard Sirtuins: guardians of mammalian healthspan Trends Genet 30 7 2014 271 286
117. M.C. Haigis, R. Mostoslavsky, K.M. Haigis, K. Fahie, D.C. Christodoulou, A.J. Murphy, and et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells Cell 126 5 2006 941 954
118. N. Ahuja, B. Schwer, S. Carobbio, D. Waltregny, B.J. North, V. Castronovo, and et al. Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase J Biol Chem 282 46 2007 33583 33592
119. L. Ho, A.S. Titus, K.K. Banerjee, S. George, W. Lin, S. Deota, and et al. SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK Aging (Albany NY) 5 11 2013 835 849
120. M.S. Jeong, C. Xiao, L.W.S. Finley, T. Lahusen, A.L. Souza, K. Pierce, and et al. SIRT4 has tumor suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism Cancer Cell 23 4 2013 450 463
121. G. Laurent, N.J. German, A.K. Saha, V.J.C. De Boer, M. Davies, T.R. Kouves, and et al. SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase Mol Cell 50 5 2013 686 698
122. L. Zhong, and R. Mostoslavsky Fine tuning our cellular factories: sirtuins in mitochondrial biology Cell Metab 13 6 2011 621 626
123. M. Gertz, and C. Steegborn Function and regulation of the mitochondrial sirtuin isoform Sirt5 in Mammalia Biochim Biophys Acta 1804 8 2010 1658 1665
124. J. Du, Y. Zhou, X. Su, J.J. Yu, S. Khan, H. Jiang, and et al. SIRT5 is a NAD-dependent protein lysine demalonylase and desuccinylase Science 334 6057 2011 806 809
125. T. Nakagawa, D.J. Lomb, M.C. Haigis, and L. Guarente SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle Cell 137 3 2009 560 570
126. M. Ogura, Y. Nakamura, D. Tanaka, X. Zhuang, Y. Fujita, A. Obara, and et al. Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1 Biochem Biophys Res Commun 393 1 2010 73 78
127. Z.F. Lin, H.B. Xu, J.Y. Wang, Q. Lin, Z. Ruan, F.B. Liu, and et al. SIRT5 desuccinylates and activates SOD1 to eliminate ROS Biochem Biophys Res Commun 441 1 2013 191 195
128. Z. Mao, C. Hine, X. Tian, M. Van Meter, M. Au, A. Vaidya, and et al. SIRT6 promotes DNA repair under stress by activating PARP1 Science 332 6036 2011 1443 1446
129. R. Mostoslavsky, K.F. Chua, D.B. Lombard, W.W. Pang, M.R. Fischer, L. Gellon, and et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6 Cell 124 2 2006 315 329
130. M. Van Meter, Z. Mao, V. Gorbunova, and A. Seluanov SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal cells Cell Cycl 10 18 2011 3153 3158
131. E. Michishita, R.A. McCord, E. Berber, M. Kioi, H. Padilla-Nash, M. Damian, and et al. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin Nature 452 7186 2008 492 496
132. E. Michishita, R.A. McCord, L.D. Boxer, M.F. Barber, T. Hong, O. Gozani, and et al. Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6 Cell Cycl 8 16 2009 2664 2666
133. H. Jiang, S. Khan, Y. Wang, G. Charron, B. He, C. Sebastian, and et al. SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine Nature 496 7443 2013 110 113
134. R. Gil, S. Barth, Y. Kanfi, and H.Y. Cohen SIRT6 exhibits nucleosome-dependent deacetylase activity Nucl Acids Res 41 18 2013 8537 8545
135. A.A. Gertler, and H.Y. Cohen SIRT6, a protein with many faces Biogerontology 14 6 2013 629 639
136. L. Min, Y. Ji, L. Bakiri, Z. Qiu, J. Cen, X. Chen, and et al. Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin Nat Cell Biol 14 11 2012 1203 1211
137. S. Nemoto, M.M. Fergusson, and T. Finkel Nutrient availability regulates SIRT1 through a forkhead-dependent pathway Science 306 5704 2004 2105 2108
138. P. Karmakar, J. Piotrowski, R.M. Brosh, J.A. Sommers, S.P. Miller, W.H. Cheng, and et al. Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation J Biol Chem 277 21 2002 18291 18302
139. B. Yang, B.M. Zwaans, M. Eckersdorff, and D.B. Lombard The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability Cell Cycl 8 16 2009 2662 2663
140. P. Huertas DNA resection in eukaryotes: deciding how to fix the break Nat Struct Mol Biol 17 1 2010 11 16
141. A.A. Sartori, C. Lukas, J. Coates, M. Mistrik, S. Fu, J. Bartek, and et al. Human CtIP promotes DNA end resection Nature 450 7169 2007 509 514
142. E.P. Mimitou, and L.S. Symington DNA end resection: many nucleases make light work DNA Repair 8 9 2009 983 995
143. A. Kaidi, B.T. Weinert, C. Choudhary, and S.P. Jackson Human SIRT6 promotes DNA end resection through CtIP deacetylation Science 329 5997 2010 1348 1353
144. S. Beneke Regulation of chromatin structure by poly (ADP-ribosyl)ation Front Genet 3 2012 169
145. R.I. Tennen, D.J. Bua, W.E. Wright, and K.F. Chua SIRT6 is required for maintenance of telomere position effect in human cells Nat Commun 2 2011 433
146. A. Cardus, A.K. Uryga, G. Walters, and J.D. Erusalimsky SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence Cardiovasc Res 97 3 2013 571 579
147. Z. Mao, X. Tian, M. Van Meter, Z. Ke, V. Gorbunova, and A. Seluanov Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence Proc Natl Acad Sci U S A 109 29 2011 11800 11805
148. C. Xiao, H.S. Kim, T. Lahusen, R.H. Wang, X. Xu, O. Gavrilova, and et al. SIRT6 deficiency results in severe hypoglycemia by enhancing both basal and insulin-stimulated glucose uptake in mice J Biol Chem 285 47 2010 36776 36784
149. T.L. Kawahara, E. Michishita, A.S. Adler, M. Damian, E. Berber, M. Lin, and et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span Cell 136 1 2009 62 74
150. L. Zhong, A. D'Urso, D. Toiber, C. Sebastian, R.E. Henry, D.D. Vadysirisack, and et al. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha Cell 140 2 2010 280 293
151. J.J. Lum, T. Bui, M. Gruber, J.D. Gordan, R.J. DeBerardinis, K.L. Covello, and et al. The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis Genes Dev 21 9 2007 1037 1049
152. T.N. Seagroves, H.E. Ryan, H. Lu, B.G. Wouters, M. Knapp, P. Thibault, and et al. Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells Mol Cell Biol 21 10 2001 3436 3444
153. E.L. Bell, B.M. Emerling, S.J. Ricoult, and L. Guarente SirT3 suppresses hypoxia-inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production Oncogene 30 26 2011 2986 2996
154. J.E. Dominy, Y. Lee, M.P. Jedrychowski, H. Chim, M.J. Jurczak, J.P. Camporez, and et al. The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis Mol Cell 48 6 2012 900 913
155. KanfiY, V. Peshti, R. Gil, S. Naiman, L. Nahum, E. Levin, and et al. SIRT6 protects against pathological damage caused by diet-induced obesity Aging Cell 9 2 2010 162 173
156. B. Schwer, B. Schumacher, D.B. Lombard, C. Xiao, M.V. Kurtev, and et al. Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity Proc Natl Acad Sci U S A 107 50 2010 21790 21794
157. Y. Kanfi, S. Naiman, G. Amir, V. Peshti, G. Zinman, L. Nahum, and et al. The sirtuin SIRT6 regulates lifespan in male mice Nature 483 7388 2012 218 221
158. R.A. Cairns, I.S. Harris, and T.W. Mak Regulation of cancer cell metabolism Nat Rev Cancer 11 2 2011 85 95
159. R. Eferl, R. Ricci, L. Kenner, R. Zenz, J.P. David, M. Rath, and et al. Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53 Cell 112 2 2003 181 192
160. M. Das, D.S. Garlick, D.L. Greiner, and R.J. Davis The role of JNK in the development of hepatocellular carcinoma Genes Dev 25 6 2011 634 645
161. C. Sebastián, B.M. Zwaans, D.M. Silberman, M. Gymrek, A. Goren, L. Zhong, and et al. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism Cell 151 6 2012 1185 1199
162. W. Ma, L.J. Stafford, D. Li, J. Luo, X. Li, G. Ning, and et al. GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis J Cell Biochem 100 6 2007 1376 1386
163. E. Ford, R. Voit, G. Liszt, C. Magin, I. Grummt, and L. Guarente Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription Genes Dev 20 2006 1075 1080
164. W. Kim, and J.E. Kim SIRT7 - an emerging sirtuin. Deciphering newer roles J Physiol Pharmacol 64 5 2013 531 534
165. S. Kiran, N. Chatterjee, S. Singh, S.C. Kaul, R. Wadhwa, and G. Ramakrishna Intracellular distribution of human SIRT7 and mapping of the nuclear/nucleolar localization signal FEBS J 280 14 2013 3451 3466
166. A. Grob, P. Roussel, J.E. Wright, B. McStay, D. Hernandez-Verdun, and V. Sirri Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis J Cell Sci 122 Pt 4 2009 489 498
167. M.F. Barber, E. Michishita-Kioi, Y. Xi, L. Tasselli, M. Kioi, Z. Moqtaderi, and et al. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation Nature 487 7405 2012 114 118
168. S. Kaikkonen, H. Makkonen, M. Rytinki, and J.J. Palvimo SUMOylation can regulate the activity of ETS-like transcription factor 4 Biochim Biophys Acta 1799 8 2010 555 560
169. C.K. Galang, W.J. Muller, G. Foos, R.G. Oshima, and C.A. Hauser Changes in the expression of many Ets family transcription factors and of potential target genes in normal mammary tissue and tumors J Biol Chem 279 12 2004 11281 11292
170. O. Vakhrusheva, D. Braeuer, Z. Liu, T. Braun, and E. Bober Sirt7-dependent inhibition of cell growth and proliferation might be instrumental to mediate tissue integrity during aging J Physiol Pharmacol 59 Suppl. 9 2008 201 212
171. O. Vakhrusheva, C. Smolka, P. Gajawada, S. Kostin, T. Boettger, T. Kubin, and et al. Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice Circ Res 102 6 2008 703 710
172. E. Michishita, J.Y. Park, J.M. Burneskis, J.C. Barrett, and I. Horikawa Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins Mol Biol Cell 16 10 2005 4623 4635
173. K.T. Howitz, K.J. Bitterman, H.Y. Cohen, D.W. Lamming, S. Lavu, J.G. Wood, and et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan Nature 425 6954 2003 191 196
174. J.G. Wood, B. Rogina, S. Lavu, K. Howitz, S.L. Helfand, M. Tatar, and et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans Nature 430 7000 2004 686 689
175. J.L. Barger, T. Kayo, T.D. Pugh, T.A. Prolla, and R. Weindruch Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart Exp Gerontol 43 9 2008 859 866
176. K.J. Pearson, J.A. Baur, K.N. Lewis, L. Peshkin, N.L. Price, N. Labinskyy, and et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span Cell Metab 8 2 2008 157 168