Sirtuin-targeting drugs: Mechanisms of action and potential therapeutic applications

Current Opinion in Investigational Drugs

Volumn 11, Issue 10, 2010, Pages 1158-1168

  Aljada, A ^a   Dong, L ^a   Mousa, S A ^b,c  

^a LONG ISLAND UNIVERSITY   (United States)

^b ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES   (United States)

^c KING SAUD UNIVERSITY   (Saudi Arabia)

Author keywords

Cancer; longevity; neurodegenerative disease; protein deacetylase; resveratrol; sirtuin; small molecule inhibitor

Indexed keywords

AC 93253; ANTIDIABETIC AGENT; ANTINEOPLASTIC AGENT; ANTIPSORIASIS AGENT; CISPLATIN; CYCLIN DEPENDENT KINASE INHIBITOR 1B; GSK 184072; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; HISTONE H3; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MANGANESE SUPEROXIDE DISMUTASE; NICOTINAMIDE; RESVERATROL; SIRTINOL; SIRTUIN; SIRTUIN 1; SIRTUIN 2; SIRTUIN 3; SIRTUIN 4; SIRTUIN 5; SIRTUIN 6; SIRTUIN 7; SRT 2104; SRT 501; SURAMIN; TRICHOSTATIN A; UNCLASSIFIED DRUG;

ABSENCE OF SIDE EFFECTS; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; APOPTOSIS; CANCER RESISTANCE; CARCINOGENESIS; CELL CYCLE ARREST; CLINICAL TRIAL; DIABETES MELLITUS; DRUG MECHANISM; DRUG SAFETY; ENERGY METABOLISM; ENZYME ACTIVITY; GLUCOSE HOMEOSTASIS; HUMAN; HUNTINGTON CHOREA; INSULIN RELEASE; LIPID METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PARKINSON DISEASE; PROTEIN LOCALIZATION; PSORIASIS; REVIEW; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; DRUG DELIVERY SYSTEMS; GROUP III HISTONE DEACETYLASES; HISTONE DEACETYLASES; HUMANS; LONGEVITY; METABOLIC DISEASES; NAD; NEURODEGENERATIVE DISEASES; SACCHAROMYCES CEREVISIAE; SIRTUINS;

EID: 77957565881     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (111)

1. Smith J: Human Sir2 and the 'silencing' of p53 activity. Trends Cell Biol (2002) 12(9):404-406.
2. Blander G, Guarente L: The Sir2 family of protein deacetylases. Annu Rev Biochem (2004) 73:417-435.
3. Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T: Human Sir2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J (2002) 21(10):2383-2396.
4. Landry J, Sutton A, Tafrov ST, Heller RC, Stebbins J, Pillus L, Sternglanz R: The silencing protein Sir2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci USA (2000) 97(11):5807-5811.
5. 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(26):14178-14182.
6. +-dependent tubulin deacetylase. Mol Cell (2003) 11(2):437-444.
7. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I: Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Bio Cell (2005) 16(10):4623-4635.
8. Westphal CH, Dipp MA, Guarente L: A therapeutic role for sirtuins in diseases of aging? Trends Biochem Sci (2007) 32(12):555-560.
9. Gan L, Mucke L: Paths of convergence: Sirtuins in aging and neurodegeneration. Neuron (2008) 58(1):10-14.
10. Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA: hSir2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell (2001) 107(2):149-159.
11. Cohen HY, Lavu S, Bitterman KJ, Hekking B, Imahiyerobo TA, Miller C, Frye R, Ploegh H, Kessler BM, Sinclair DA: Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis. Mol Cell (2004) 13(5):627-638.
12. Han SH: Potential role of sirtuin as a therapeutic target for neurodegenerative diseases. J Clin Neurol (2009) 5(3): 120-125.
13. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS et al: Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science (2004) 303(5666):2011-2015.
14. Daitoku H, Hatta M, Matsuzaki H, Aratani S, Ohshima T, Miyagishi M, Nakajima T, Fukamizu A: Silent information regulator 2 potentiates FOXO1-mediated transcription through its deacetylase activity. Proc Natl Acad Sci USA (2004) 101(27):10042-10047.
15. Cheng HL, Mostoslavsky R, Saito S, Manis JP, Gu Y, Patel P, Bronson R, Appella E, Alt FW, Chua KF: Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Proc Natl Acad Sci USA (2003) 100(19):10794-10799.
16. McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, Webb JR, Lansdorp PM, Lemieux M: The mammalian Sir2α protein has a role in embryogenesis and gametogenesis. Mol Cell Biol (2003) 23(1):38-54.
17. Lamming DW, Latorre-Esteves M, Medvedik O, Wong SN, Tsang FA, Wang C, Lin SJ, Sinclair DA: HST2 mediates Sir2-independent life-span extension by calorie restriction. Science (2005) 309(5742):1861-1864.
18. 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(9):3173-3185.
19. Vaquero A, Scher MB, Lee DH, Sutton A, Cheng HL, Alt FW, Serrano L, Sternglanz R, Reinberg D: SIRT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev (2006) 20(10):1256-1261.
20. Wang Y, Tissenbaum HA: Overlapping and distinct functions for a Caenorhabditis elegans Sir2 and DAF-16/FOXO. Mech Ageing Dev (2006) 127(1):48-56.
21. Shi T, Wang F, Stieren E, Tong Q: SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem (2005) 280(14):13560-13567.
22. 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(21):13653-13658.
23. 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(4):647-657.
24. 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(27):10224-10229.
25. Hallows WC, Lee S, Denu JM: Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci USA (2006) 103(27):10230-10235.
26. Rose G, Dato S, Altomare K, Bellizzi D, Garasto S, Greco V, Passarino G, Feraco E, Mari V, Barbi C, BonaFe M et al: Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Exp Gerontol (2003) 38(10):1065-1070.
27. Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C et al: SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic β cells. Cell (2006) 126(5):941-954.
28. 32P-NAD. Biochemistry (2009) 48(13):2878-2890.
29. Nakagawa T, Lomb DJ, Haigis MC, Guarente L: SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell (2009) 137(3):560-570.
30. Liszt G, Ford E, Kurtev M, Guarente L: Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem (2005) 280(22):21313-21320.
31. Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD et al: Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell (2006) 124(2):315-329.
32. Lombard DB, Schwer B, Alt FW, Mostoslavsky R: SIRT6 in DNA repair, metabolism and ageing. J Intern Med (2008) 263(2):128-141.
33. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF: SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell (2009) 136(1):62-74.
34. Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B, Wikstrom JD, Nir T, Clish CB et al: The histone deacetylase SIRT6 regulates glucose homeostasis via HIF1α. Cell (2010) 140(2):280-293.
35. Frye RA: Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun (2000) 273(2):793-798.
36. Ford E, Voit R, Liszt G, Magin C, Grummt I, Guarente L: Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev (2006) 20(9):1075-1080.
37. Grummt I, Pikaard CS: Epigenetic silencing of RNA polymerase I transcription. Nat Rev Mol Cell Biol (2003) 4(8): 641-649.
38. Zhao Y, Sohn JH, Warner JR: Autoregulation in the biosynthesis of ribosomes. Mol Cell Biol (2003) 23(2):699-707.
39. Vakhrusheva O, Smolka C, Gajawada P, Kostin S, Boettger T, Kubin T, Braun T, Bober E: SIRT7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ Res (2008) 102(6):703-710.
40. Hursting SD, Perkins SN, Phang JM, Barrett JC: Diet and cancer prevention studies in p53-deficient mice. J Nutr (2001) 131(11 Suppl):3092S-3094S.
41. Lin SJ, Defossez PA, Guarente L: Requirement of NAD and Sir2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science (2000) 289(5487): 2126-2128.
42. Rogina B, Helfand SL: Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA (2004) 101(45):15998-16003.
43. Berrigan D, Perkins SN, Haines DC, Hursting SD: Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. Carcinogenesis (2002) 23(5):817-822.
44. Lane MA, Ingram DK, Roth GS: Calorie restriction in nonhuman primates: Effects on diabetes and cardiovascular disease risk. Toxicol Sci (1999) 52(2 Suppl):41-48.
45. Masoro EJ: Caloric restriction and aging: An update. Exp Gerontol (2000) 35(3):299-305.
46. Stern JS, Gades MD, Wheeldon CM, Borchers AT: Calorie restriction in obesity: Prevention of kidney disease in rodents. J Nutr (2001) 131(3):913S-917S.
47. Fontana L, Klein S: Aging, adiposity, and calorie restriction. JAMA (2007) 297(9):986-994.
48. Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, Culotta VC, Fink GR, Guarente L: Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature (2002) 418(6895):344-348. (Pubitemid 34790687)
49. Dhahbi JM, Mote PL, Wingo J, Rowley BC, Cao SX, Walford RL, Spindler SR: Caloric restriction alters the feeding response of key metabolic enzyme genes. Mech Ageing Dev (2001) 122(10):1033-1048.
50. Moynihan KA, Grimm AA, Plueger MM, Bernal-Mizrachi E, Ford E, Cras-Méneur C, Permutt MA, Imai S: Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice. Cell Metab (2005) 2(2): 105-117.
51. Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J, McDonagh T, Lemieux M, McBurney M, Szilvasi A, Easlon E et al: SIRT1 regulates insulin secretion by repressing UCP2 in pancreatic β cells. PLoS Biol (2006) 4(2):e31.
52. Chen D, Steele AD, Lindquist S, Guarente L: Increase in activity during calorie restriction requires SIRT1. Science (2005) 310(5754):1641.
53. Wang F, Nguyen M, Qin FX, Tong Q: SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell (2007) 6(4):505-514.
54. Kanfi Y, Shalman R, Peshti V, Pilos of SN, Gozlan YM, Pearson KJ, Lerrer B, Moazed D, Marine JC, de Cabo R, Cohen HY: Regulation of SIRT6 protein levels by nutrient availability. FEBS Lett (2008) 582(5):543-548.
55. Kanfi Y, Peshti V, Gil R, Naiman S, Nahum L, Levin E, Kronfeld-Schor N, Cohen HY: SIRT6 protects against pathological damage caused by diet-induced obesity. Aging Cell (2010) 9(2):162-173.
56. 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(3):437-448.
57. Chu F, Chou PM, Zheng X, Mirkin BL, Rebbaa A: Control of multidrug resistance gene mdr1 and cancer resistance to chemotherapy by the longevity gene sirt1. Cancer Res (2005) 65(22):10183-10187.
58. Liang XJ, Finkel T, Shen DW, Yin JJ, Aszalos A, Gottesman MM: SIRT1 contributes in part to cisplatin resistance in cancer cells by altering mitochondrial metabolism. Mol Cancer Res (2008) 6(9):1499-1506.
59. Kojima K, Ohhashi R, Fujita Y, Hamada N, Akao Y, Nozawa Y, Deguchi T, Ito M: A role for SIRT1 in cell growth and chemoresistance in prostate cancer PC3 and DU145 cells. Biochem Biophys Res Commun (2008) 373(3):423-428.
60. Hiratsuka M, Inoue T, Toda T, Kimura N, Shirayoshi Y, Kamitani H, Watanabe T, Ohama E, Tahimic CG, Kurimasa A, Oshimura M: Proteomics-based identification of differentially expressed genes in human gliomas: Down-regulation of SIRT2 gene. Biochem Biophys Res Commun (2003) 309(3):558-566.
61. 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(4):729-733.
62. Ashraf N, Zino S, Macintyre A, Kingsmore D, Payne AP, George WD, Shiels PG: Altered sirtuin expression is associated with node-positive breast cancer. Br J Cancer (2006) 95(8):1056-1061.
63. Pallas M, Verdaguer E, Tajes M, Gutierrez-Cuesta J, Camins A: Modulation of sirtuins: New targets for antiageing. Recent Pat CNS Drug Discov (2008) 3(1):61-69.
64. Tang BL, Chua CE: SIRT1 and neuronal diseases. Mol Aspects Med (2008) 29(3):187-200.
65. Araki T, Sasaki Y, Milbrandt J: Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science (2004) 305(5686):1010-1013.
66. Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE: Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease. Neurochem Int (2009) 54(2):111-118.
67. 231-phosphotau. J Neurosci (2008) 28(45):11500-11510.
68. Li W, Zhang B, Tang J, Cao Q, Wu Y, Wu C, Guo J, Ling EA, Liang F: Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating α-tubulin. J Neurosci (2007) 27(10): 2606-2616.
69. Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, Young AB et al: Sirtuin 2 inhibitors rescue α-synuclein-mediated toxicity in models of Parkinson's disease. Science (2007) 317(5837):516-519.
70. Luthi-Carter R, Taylor DM, Pallos J, Lambert E, Amore A, Parker A, Moffitt H, Smith DL, Runne H, Gokce O, Kuhn A et al: SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci USA (2010) 107(17): 7927-7932.
71. Pfister JA, Ma C, Morrison BE, D'Mello SR: Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity. PLoS One (2008) 3(12):e4090.
72. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B et al: Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature2 (2003) 425(6954): 191-196.
73. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D: Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature (2004) 430(7000):686-689.
74. Yang H, Baur JA, Chen A, Miller C, Adams JK, Kisielewski A, Howitz KT, Zipkin RE, Sinclair DA: Design and synthesis of compounds that extend yeast replicative lifespan. Aging Cell (2007) 6(1):35-43.
75. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ et al: Resveratrol improves health and survival of mice on a high-calorie diet. Nature (2006) 444(7117):337-342.
76. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B et al: Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell (2006) 127(6):1109-1122.
77. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE et al: Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature (2007) 450(7170):712-716.
78. Sirtris Pharmaceuticals Inc: Sirtris Pharmaceuticals initiates phase 2a clinical trial in patients with type 2 diabetes. Press Release (2007): August 21.
79. February 2010 - Product Development Pipeline: GlaxoSmithKline plc, Brentford, Middlesex, UK (2010). www.gsk.com/investors/product-pipeline/docs/ GSK-product-pipeline-Feb-2010.pdf
80. Marques FZ, Markus MA, Morris BJ: Resveratrol: Cellular actions of a potent natural chemical that confers a diversity of health benefits. Int J Biochem Cell Biol (2009) 41(11): 2125-2128.
81. Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M: Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des (2009) 74(6):619-624.
82. Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, Griffith D, Griffor M, Loulakis P, Pabst B, Qiu X et al: SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem (2010) 285(11): 8340-8351.
83. Calamini B, Ratia K, Malkowski MG, Cuendet M, Pezzuto JM, Santarsiero BD, Mesecar AD: Pleiotropic mechanisms facilitated by resveratrol and its metabolites. Biochem J (2010) 429(2):273-282.
84. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA et al: Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab (2008) 8(2):157-168.
85. Lavu S, Boss O, Elliott PJ, Lambert PD: Sirtuins - Novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov (2008) 7(10):841-853.
86. Pillarisetti S: A review of SIRT1 and SIRT1 modulators in cardiovascular and metabolic diseases. Recent Pat Cardiovasc Drug Discov (2008) 3(3):156-164.
87. Nayagam VM, Wang X, Tan YC, Poulsen A, Goh KC, Ng T, Wang H, Song HY, Ni B, Entzeroth M, Stünkel W: SIRT1 modulating compounds from high-throughput screening as anti-inflammatory and insulin-sensitizing agents. J Biomol Screen (2006) 11(8):959-967.
88. Lain S, Hollick JJ, Campbell J, Staples OD, Higgins M, Aoubala M, McCarthy A, Appleyard V, Murray KE, Baker L, Thompson A et al: Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell (2008) 13(5):454-463.
89. Denu JM: The Sir 2 family of protein deacetylases. Curr Opin Chem Biol (2005) 9(5):431-440.
90. Imai S, Armstrong CM, Kaeberlein M, Guarente L: Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature (2000) 403(6771):795-800.
91. Amat R, Planavila A, Chen SL, Iglesias R, Giralt M, Villarroya F: SIRT1 controls the transcription of the peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) gene in skeletal muscle through the PGC-1α autoregulatory loop and interaction with MyoD. J Biol Chem (2009) 284(33): 21872-21880.
92. Bouras T, Fu M, Sauve AA, Wang F, Quong AA, Perkins ND, Hay RT, Gu W, Pestell RG: SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J Biol Chem (2005) 280(11): 10264-10276.
93. Chen Z, Peng IC, Cui X, Li YS, Chien S, Shyy JY: Shear stress, SIRT1, and vascular homeostasis. Proc Natl Acad Sci USA (2010) 107(22):10268-10273.
94. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA: Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science (2004) 305(5682):390-392.
95. Dai JM, Wang ZY, Sun DC, Lin RX, Wang SQ: SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity. J Cell Physiol (2007) 210(1):161-166.
96. Kim JE, Chen J, Lou Z: DBC1 is a negative regulator of SIRT1. Nature (2008) 451(7178):583-586.
97. Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isono M, Isshiki K, Uzu T, Kashiwagi A, Koya D: Silent information regulator 2 (SIRT1) attenuates oxidative stress-induced mesangial cell apoptosis via p53 deacetylation. Free Radic Biol Med (2006) 40(12):2175-2182.
98. Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isshiki K, Isono M, Uzu T, Guarente L, Kashiwagi A, Koya D: SIRT1 inhibits transforming growth factor p-induced apoptosis in glomerular mesangial cells via SMAD7 deacetylation. J Biol Chem (2007) 282(1):151-158.
99. 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(1):91-106.
100. Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J 3rd, Olefsky J et al: A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature (2008) 456(7219): 269-273.
101. Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W: Negative control of p53 by Sir2 promotes cell survival under stress. Cell (2001) 107(2):137-148.
102. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L: SIRT1 promotes fat mobilization in white adipocytes by repressing PPAR-γ. Nature (2004) 429(6993):771-776.
103. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P: Nutrient control of glucose homeostasis through a complex of PGC-1 and SIRT1. Nature (2005) 434(7029):113-118.
104. SIRT1. J Biol Chem (2004) 279(28):28873-28879.
105. Vaquero A, Scher M, Erdjument-Bromage H, Tempst P, Serrano L, Reinberg D: SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Nature (2007) 450(7168):440-444.
106. Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D: Human SIRT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol Cell (2004) 16(1):93-105.
107. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW: Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J (2004) 23(12):2369-2380.
108. I68, a subunit of TIF-IB/SL1, activates RNA polymerase I transcription. EMBO J (2001) 20(6):1353-1362.
109. Jin YH, Kim YJ, Kim DW, Baek KH, Kang BY, Yeo CY, Lee KY: SIRT2 interacts with 14-3-3 β/γ and down-regulates the activity of p53. Biochem Biophys Res Commun (2008) 368(3): 690-695.
110. Palacios OM, Carmona JJ, Michan S, Chen KY, Manabe Y, Ward JL 3rd, Goodyear LJ, Tong Q: Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1 in skeletal muscle. Aging (Albany NY) (2009) 1(9):771-783.
111. Ahuja N, Schwer B, Carobbio S, Waltregny D, North BJ, Castronovo V, Maechler P, Verdin E: Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J Biol Chem (2007) 282(46):33583-33592.