Targeting sirtuin 1 to improve metabolism: All you need is NAD +?

Pharmacological Reviews

Volumn 64, Issue 1, 2012, Pages 166-187

  Cantó, Carles ^a   Auwerx, Johan ^a  

^a EPFL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL COENZYME A DESATURASE 1; ADIPONECTIN; CD157 ANTIGEN; CD38 ANTIGEN; CHOLESTEROL 7ALPHA MONOOXYGENASE; FIBROBLAST GROWTH FACTOR 21; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; LEPTIN; LIVER X RECEPTOR; LIVER X RECEPTOR ALPHA; LIVER X RECEPTOR BETA; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 2; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PROTEIN P21; PROTEIN P53; RECEPTOR INTERACTING PROTEIN 140; SIRTUIN 1; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TRANSCRIPTION FACTOR FKHR; TRANSCRIPTION FACTOR FKHRL1; TRANSCRIPTION FACTOR FOXO;

APOPTOSIS; BIOSYNTHESIS; DISEASE ASSOCIATION; DNA DAMAGE; DRUG TARGETING; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME SYNTHESIS; FATTY LIVER; GLUCOSE TOLERANCE; HUMAN; HYPERGLYCEMIA; LEAN BODY WEIGHT; METABOLIC DISORDER; METABOLIC REGULATION; METABOLISM; MITOCHONDRIAL RESPIRATION; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; SUMOYLATION;

ANIMALS; DRUG DISCOVERY; ENERGY METABOLISM; HUMANS; METABOLIC DISEASES; NAD; PROTEIN CONFORMATION; SIRTUIN 1; SUBSTRATE SPECIFICITY;

EID: 83455206803     PISSN: 00316997     EISSN: 15210081     Source Type: Journal    
DOI: 10.1124/pr.110.003905     Document Type: Review

References (234)

1. Aksoy P, Escande C, White TA, Thompson M, Soares S, Benech JC, and Chini EN (2006) Regulation of SIRT 1 mediated NAD dependent deacetylation: a novel role for the multifunctional enzyme CD38. Biochem Biophys Res Commun 349:353-359.
2. Altarejos JY and Montminy M (2011) CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nat Rev Mol Cell Biol 12:141-151.
3. Altschul R, Hoffer A, and Stephen JD (1955) Influence of nicotinic acid on serum cholesterol in man. Arch Biochem Biophys 54:558-559.
4. Amé JC, Rolli V, Schreiber V, Niedergang C, Apiou F, Decker P, Muller S, Hoger T, Ménissier-demurcia J, and de Murcia G (1999) PARP-2, a novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J Biol Chem 274:17860-17868
5. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, and Sinclair DA (2003) Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423:181-185.
6. Araki T, Sasaki Y, and Milbrandt J (2004) Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305:1010-1013.
7. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, Mostoslavsky R, Alt FW, and Schibler U (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134:317-328.
8. Asher G, Reinke H, Altmeyer M, Gutierrez-Arcelus M, Hottiger MO, and Schibler U (2010) Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. Cell 142:943-953.
9. Bai P, Canto C, Brunyánszki A, Huber A, Szántó M, Cen Y, Yamamoto H, Houten SM, Kiss B, Oudart H, et al. (2011a) PARP-2 regulates SIRT1 expression and whole-body energy expenditure. Cell Metab 13:450-460.
10. Bai P, Cantó C, Oudart H, Brunyánszki A, Cen Y, Thomas C, Yamamoto H, Huber A, Kiss B, Houtkooper RH, et al. (2011b) PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab 13:461-468
11. Bai P, Houten SM, Huber A, Schreiber V, Watanabe M, Kiss B, de Murcia G, Auwerx J, and Ménissier-demurcia J (2007) Poly(ADP-ribose) polymerase-2 [corrected] controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid X receptor/peroxisome proliferator-activated receptor-gamma [corrected] heterodimer. J Biol Chem 282:37738-37746.
12. Banks AS, Kon N, Knight C, Matsumoto M, Gutiérrez-Juárez R, Rossetti L, Gu W, and Accili D (2008) SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Cell Metab 8:333-341.
13. Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, et al. (2008) A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE 3:e2264.
14. Bauer JH, Morris SN, Chang C, Flatt T, Wood JG, and Helfand SL (2009) dSir2 and Dmp53 interact to mediate aspects of CR-dependent lifespan extension in D. melanogaster. Aging (Albany NY) 1:38-48.
15. Baur JA (2010) Resveratrol, sirtuins, and the promise of a DR mimetic. Mech Ageing Dev 131:261-269
16. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, et al. (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337-342.
17. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, and Gygi SP (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci USA 101:12130-12135.
18. Belenky P, Racette FG, Bogan KL, McClure JM, Smith JS, and Brenner C (2007) Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD. Cell 129:473-484.
19. Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nusing RM, Moers A, Pfeffer K, and Offermanns S (2005) GPR109A (PUMA-G/HM74A) mediates nicotinic acidinduced flushing. J Clin Invest 115:3634-3640.
20. Berdichevsky A, Viswanathan M, Horvitz HR, and Guarente L (2006) C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell 125:1165-1177.
21. Bieganowski P and Brenner C (2004) Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD in fungi and humans. Cell 117:495-502.
22. Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, and Sinclair DA (2002) Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem 277:45099-45107
23. Boily G, Seifert EL, Bevilacqua L, He XH, Sabourin G, Estey C, Moffat C, Crawford S, Saliba S, Jardine K, et al. (2008) SirT1 regulates energy metabolism and response to caloric restriction in mice. PLoS One 3:e1759.
24. Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, Czopik A, Steele AD, Crowe H, Marmor S, Luo J, et al. (2007) SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6:759-767.
25. Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J, McDonagh T, Lemieux M, McBurney M, Szilvasi A, et al. (2006) Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol 4:e31.
26. Borra MT, Smith BC, and Denu JM (2005) Mechanism of human SIRT1 activation by resveratrol. J Biol Chem 280:17187-17195.
27. Bouras T, Fu M, Sauve AA, Wang F, Quong AA, Perkins ND, Hay RT, Gu W, and Pestell RG (2005) SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J Biol Chem 280: 10264-10276.
28. Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Poljak A, and Grant R (2011) Age related changes in NAD metabolism oxidative stress and Sirt1 activity in wistar rats. PLoS One 6:e19194.
29. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, et al. (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303:2011-2015
30. Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvári M, Piper MD, Hoddinott M, Sutphin GL, Leko V, McElwee JJ, et al. (2011) Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477:482-485.
31. Cakir-Kiefer C, Muller-Steffner H, Oppenheimer N, and Schuber F (2001) Kinetic competence of the cADP-ribose-CD38 complex as an intermediate in the CD38/ NAD glycohydrolase-catalysed reactions: implication for CD38 signalling. Biochem J 358:399-406.
32. Cantó C and Auwerx J (2009) Caloric restriction, SIRT1 and longevity. Trends Endocrinol Metab 20:325-331.
33. Cantó C and Auwerx J (2010) AMP-activated protein kinase and its downstream transcriptional pathways. Cell Mol Life Sci 67:3407-3423.
34. Cantó C and Auwerx J (2011) Interference between PARPs and SIRT1: a novel approach to healthy ageing? Aging (Albany NY) 3:543-547.
35. Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, and Auwerx J (2009) AMPK regulates energy expenditure by modulating NAD metabolism and SIRT1 activity. Nature 458:1056-1060
36. Cantó C, Jiang LQ, Deshmukh AS, Mataki C, Coste A, Lagouge M, Zierath JR, and Auwerx J (2010) Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 11:213-219.
37. Cohen DE, Supinski AM, Bonkowski MS, Donmez G, and Guarente LP (2009) Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction. Genes Dev 23:2812-2817.
38. Collins PB and Chaykin S (1972) The management of nicotinamide and nicotinic acid in the mouse. J Biol Chem 247:778-783.
39. Costa Cdos S, Hammes TO, Rohden F, Margis R, Bortolotto JW, Padoin AV, Mottin CC, and Guaragna RM (2010) SIRT1 transcription is decreased in visceral adipose tissue of morbidly obese patients with severe hepatic steatosis. Obes Surg 20:633-639.
40. Coste A, Louet JF, Lagouge M, Lerin C, Antal MC, Meziane H, Schoonjans K, Puigserver P, O'Malley BW, and Auwerx J (2008) The genetic ablation of SRC-3 protects against obesity and improves insulin sensitivity by reducing the acetylation of PGC-1{alpha}. Proc Natl Acad Sci USA 105:17187-17192.
41. Costford SR, Bajpeyi S, Pasarica M, Albarado DC, Thomas SC, Xie H, Church TS, Jubrias SA, Conley KE, and Smith SR (2010) Skeletal muscle NAMPT is induced by exercise in humans. Am J Physiol Endocrinol Metab 298:E117-E126.
42. Chambon P, Weill JD, and Mandel P (1963) Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem Biophys Res Commun 11:39-43.
43. Chau MD, Gao J, Yang Q, Wu Z, and Gromada J (2010) Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc Natl Acad Sci USA 107:12553-12558.
44. Chen D, Bruno J, Easlon E, Lin SJ, Cheng HL, Alt FW, and Guarente L (2008) Tissue-specific regulation of SIRT1 by calorie restriction. Genes Dev 22:1753-1757
45. Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, and Gan L (2005a) SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J Biol Chem 280:40364-40374.
46. Chen WY, Wang DH, Yen RC, Luo J, Gu W, and Baylin SB (2005b) Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell 123:437-448.
47. Dali-Youcef N, Lagouge M, Froelich S, Koehl C, Schoonjans K, and Auwerx J (2007) Sirtuins: the 'magnificent seven', function, metabolism and longevity. Ann Med 39:335-345.
48. Dasgupta B and Milbrandt J (2007) Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci USA 104:7217-7222.
49. De Flora A, Guida L, Franco L, and Zocchi E (1997) The CD38/cyclic ADP-ribose system: a topological paradox. Int J Biochem Cell Biol 29:1149-1166.
50. Defossez PA, Prusty R, Kaeberlein M, Lin SJ, Ferrigno P, Silver PA, Keil RL, and Guarente L (1999) Elimination of replication block protein Fob1 extends the life span of yeast mother cells. Mol Cell 3:447-455.
51. Dong M, Si YQ, Sun SY, Pu XP, Yang ZJ, Zhang LR, Zhang LH, Leung FP, Lam CM, Kwong AK, et al. (2011) Design, synthesis and biological characterization of novel inhibitors of CD38. Org Biomol Chem 9:3246-3257.
52. Donmez G, Wang D, Cohen DE, and Guarente L (2010) SIRT1 suppresses beta amyloid production by activating the alpha-secretase gene ADAM10. Cell 142: 320-332.
53. Dousa TP, Chini EN, and Beers KW (1996) Adenine nucleotide diphosphates: emerg ing second messengers acting via intracellular Ca2 z release. Am J Physiol 271: C1007-C1024.
54. Du J, Xhou Y, Su X, Yu J, Khan S, Jian H, Kim J, Woo J, Kim JH, Choi BH, et al. (2011) Sirt5 is an NAD-dependent protein lysine demalonylase and desuccinylase. Science 334:806-809.
55. Escande C, Chini CC, Nin V, Dykhouse KM, Novak CM, Levine J, van Deursen J, Gores GJ, Chen J, Lou Z, et al. (2010) Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice. J Clin Invest 120:545-558.
56. Feige JN, Lagouge M, Canto C, Strehle A, Houten SM, Milne JC, Lambert PD, Mataki C, Elliott PJ, and Auwerx J (2008) Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab 8:347-358.
57. Finkel T, Deng CX, and Mostoslavsky R (2009) Recent progress in the biology and physiology of sirtuins. Nature 460:587-591
58. Fulco M, Cen Y, Zhao P, Hoffman EP, McBurney MW, Sauve AA, and Sartorelli V (2008) Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell 14:661-673
59. Gao J, Wang WY, Mao YW, Graff J, Guan JS, Pan L, Mak G, Kim D, Su SC, and Tsai LH (2010) A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 466:1105-1109.
60. Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, and Puigserver P (2007) Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J 26:1913-1923
61. Giandomenico V, Simonsson M, Gronroos E, and Ericsson J (2003) Coactivatordependent acetylation stabilizes members of the SREBP family of transcription factors. Mol Cell Biol 23:2587-2599.
62. Goodwin PM, Lewis PJ, Davies MI, Skidmore CJ, and Shall S (1978) The effect of gamma radiation and neocarzinostatin on NAD and ATP levels in mouse leukaemia cells. Biochim Biophys Acta 543:576-582.
63. Greer EL and Brunet A (2008) FOXO transcription factors in ageing and cancer. Acta Physiol (Oxf) 192:19-28.
64. Greer EL, Oskoui PR, Banko MR, Maniar JM, Gygi MP, Gygi SP, and Brunet A (2007) The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. J Biol Chem 282:30107-30119
65. Gross CJ and Henderson LM (1983) Digestion and absorption of NAD by the small intestine of the rat. J Nutr 113:412-420.
66. Gross DN, van den Heuvel AP, and Birnbaum MJ (2008) The role of FoxO in the regulation of metabolism. Oncogene 27:2320-2336.
67. Guarente L (2000) Sir2 links chromatin silencing, metabolism, and aging. Genes Dev 14:1021-1026.
68. Guarente L (2011) Franklin H. Epstein Lecture: Sirtuins, aging, and medicine. N Engl J Med 364:2235-2244.
69. Guo X, Williams JG, Schug TT, and Li X (2010) DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. J Biol Chem 285: 13223-13232.
70. Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, et al. (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126:941-954.
71. Hallows WC, Lee S, and Denu JM (2006) Sirtuins deacetylate and activate mam malian acetyl-CoA synthetases. Proc Natl Acad Sci USA 103:10230-10235.
72. Han L, Zhou R, Niu J, McNutt MA, Wang P, and Tong T (2010) SIRT1 is regulated by a PPAR{}-SIRT1 negative feedback loop associated with senescence. Nucleic Acids Res 38:7458-7471.
73. Hara N, Yamada K, Shibata T, Osago H, Hashimoto T, and Tsuchiya M (2007) Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells. J Biol Chem 282:24574-24582
74. Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774-785.
75. Hariharan N, Maejima Y, Nakae J, Paik J, Depinho RA, and Sadoshima J (2010) Deacetylation of FoxO by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in Cardiac Myocytes. Circ Res 107:1470-1482
76. Hasmann M and Schemainda I (2003) FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res 63:7436-7442.
77. Hawley SA, Ross FA, Chevtzoff C, Green KA, Evans A, Fogarty S, Towler MC, Brown LJ, Ogunbayo OA, Evans AM, et al. (2010) Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab 11:554-565.
78. Hayashida S, Arimoto A, Kuramoto Y, Kozako T, Honda S, Shimeno H, and Soeda S (2010) Fasting promotes the expression of SIRT1, an NAD-dependent protein deacetylase, via activation of PPARalpha in mice. Mol Cell Biochem 339:285-292
79. Heikkinen S, Auwerx J, and Argmann CA (2007) PPARgamma in human and mouse physiology. Biochim Biophys Acta 1771:999-1013.
80. Herranz D, Mũoz-Martin M, Cãnamero M, Mulero F, Martinez-Pastor B, Fernandez Capetillo O, and Serrano M (2010a) Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat Commun 1:3.
81. Herranz D and Serrano M (2010) SIRT1: recent leszsons from mouse models. Nat Rev Cancer 10:819-823.
82. Herzig S, Long F, Jhala US, Hedrick S, Quinn R, Bauer A, Rudolph D, Schutz Goon C, Puigserver P, et al. (2001) CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 413:179-183.
83. Herzog B, Hall RK, Wang XL, Waltner-Law M, and Granner DK (2004) Peroxisome proliferator-activated receptor gamma coactivator-1alpha, as a transcription amplifier, is not essential for basal and hormone-induced phosphoenolpyruvate carboxykinase gene expression. Mol Endocrinol 18:807-819.
84. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, and Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333-336.
85. Houtkooper RH, Cantó C, Wanders RJ, and Auwerx J (2010) The secret life of NAD: an old metabolite controlling new metabolic signaling pathways. Endocr Rev 31:194-223.
86. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, et al. (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191-196
87. Imai S, Armstrong CM, Kaeberlein M, and Guarente L (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403:795-800.
88. Ivy JM, Klar AJ, and Hicks JB (1986) Cloning and characterization of four SIR genes of Saccharomyces cerevisiae. Mol Cell Biol 6:688-702
89. Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, Yamaguchi M, Namiki S, Nakayama R, Tabata M, et al. (2010) Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2) and AMPK/SIRT1. Nature 464:1313-1319.
90. Jackson TM, Rawling JM, Roebuck BD, and Kirkland JB (1995) Large supplements of nicotinic acid and nicotinamide increase tissue NAD and poly(ADP-ribose) levels but do not affect diethylnitrosamine-induced altered hepatic foci in Fischer-344 rats. J Nutr 125:1455-1461.
91. Jager S, Handschin C, St-Pierre J, and Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 104:12017-12022.
92. Jing E, Gesta S, and Kahn CR (2007) SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab 6:105-114.
93. Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, et al. (2005) Substrate-specific activation of sirtuins by resveratrol. J Biol Chem 280:17038-17045.
94. Kaeberlein M, McVey M, and Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570-2580.
95. Kaeberlein M and Powers RW 3rd (2007) Sir2 and calorie restriction in yeast: a skeptical perspective. Ageing Res Rev 6:128-140.
96. Kalaany NY and Mangelsdorf DJ (2006) LXRS and FXR: the yin and yang of cholesterol and fat metabolism. Annu Rev Physiol 68:159-191.
97. Kamanna VS and Kashyap ML (2008) Mechanism of action of niacin. Am J Cardiol 101:20B-26B.
98. Kang H, Jung JW, Kim MK, and Chung JH (2009) CK2 is the regulator of SIRT1 substrate-binding affinity, deacetylase activity and cellular response to DNAdamage. PLoS One 4:e6611.
99. Kapur S, Bédard S, Marcotte B, Côté CH, and Marette A (1997) Expression of nitric oxide synthase in skeletal muscle: a novel role for nitric oxide as a modulator of insulin action. Diabetes 46:1691-1700.
100. Karpe F and Frayn KN (2004) The nicotinic acid receptor-a new mechanism for an old drug. Lancet 363:1892-1894.
101. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, et al. (2007a) SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J 26:3169-3179.
102. Kim EJ, Kho JH, Kang MR, and Um SJ (2007b) Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity. Mol Cell 28:277-290.
103. Kim JE, Chen J, and Lou Z (2008) DBC1 is a negative regulator of SIRT1. Nature 451:583-586.
104. Kirkland JB (2009) Niacin status, NAD distribution and ADP-ribose metabolism. Curr Pharm Des 15:3-11.
105. Koo SH, Flechner L, Qi L, Zhang X, Screaton RA, Jeffries S, Hedrick S, Xu W, Boussouar F, Brindle P, et al. (2005) The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 437:1109-1111
106. Krishnakumar R and Kraus WL (2010) The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol Cell 39:8-24
107. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, et al. (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC1alpha. Cell 127:1109-1122.
108. Le Gouill E, Jimenez M, Binnert C, Jayet PY, Thalmann S, Nicod P, Scherrer U, and Vollenweider P (2007) Endothelial nitric oxide synthase (eNOS) knockout mice have defective mitochondrial beta-oxidation. Diabetes 56:2690-2696
109. Lee HC (2006) Structure and enzymatic functions of human CD38. Mol Med 12:317-323.
110. Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, Tsokos M, Alt FW, and Finkel T (2008) A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA 105:3374-3379
111. Lee J, Padhye A, Sharma A, Song G, Miao J, Mo YY, Wang L, and Kemper JK (2010) A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition. J Biol Chem 285:12604-12611.
112. Lerin C, Rodgers JT, Kalume DE, Kim SH, Pandey A, and Puigserver P (2006) GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1alpha. Cell Metab 3:429-438.
113. Li J, Hu X, Selvakumar P, Russell RR, 3rd, Cushman SW, Holman GD, and Young LH (2004) Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol Endocrinol Metab 287:E834-E841.
114. Li L, Pan R, Li R, Niemann B, Aurich AC, Chen Y, and Rohrbach S (2011) Mito chondrial biogenesis and PGC-1{alpha} deacetylation by physical activity: intact adipocytokine-signaling is required. Diabetes 60:157-167.
115. Li X, Zhang S, Blander G, Tse JG, Krieger M, and Guarente L (2007) SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell 28:91-106.
116. Lin SJ, Ford E, Haigis M, Liszt G, and Guarente L (2004) Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev 18:12-16.
117. Liszt G, Ford E, Kurtev M, and Guarente L (2005) Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem 280:21313-21320
118. Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J, et al. (2008) A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 456:269-273.
119. Lombard DB, Pletcher SD, Cantó C, and Auwerx J (2011) Ageing: longevity hits a roadblock. Nature 477:410-411
120. Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, and Gu W (2001) Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107:137-148.
121. Mair W, Morantte I, Rodrigues AP, Manning G, Montminy M, Shaw RJ, and Dillin A (2011) Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470:404-408.
122. Mangerich A, Herbach N, Hanf B, Fischbach A, Popp O, Moreno-Villanueva M, Bruns OT, and Burkle A (2010) Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1. Mech Ageing Dev 131:389-404
123. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, and Hwang PM (2006) p53 regulates mitochondrial respiration. Science 312: 1650-1653.
124. Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, DeRicco J, Kasuno K, and Irani K (2007) SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci USA 104:14855-14860.
125. McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, Webb JR, Lansdorp PM, and Lemieux M (2003) The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol 23:38-54.
126. Mendoza-Alvarez H and Alvarez-Gonzalez R (1993) Poly(ADP-ribose) polymerase is a catalytic dimer and the automodification reaction is intermolecular. J Biol Chem 268:22575-22580.
127. Michán S, Li Y, Chou MM, Parrella E, Ge H, Long JM, Allard JS, Lewis K, Miller M, Xu W, et al. (2010) SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci 30:9695-9707.
128. Michan S and Sinclair D (2007) Sirtuins in mammals: insights into their biological function. Biochem J 404:1-13.
129. Michishita E, McCord RA, Berber E, Kioi M, Padilla-Nash H, Damian M, Cheung P, Kusumoto R, Kawahara TL, Barrett JC, et al. (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452:492-496
130. Michishita E, Park JY, Burneskis JM, Barrett JC, and Horikawa I (2005) Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 16:4623-4635.
131. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, et al. (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450:712-716.
132. Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, and Guarente L (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116:551-563.
133. Moynihan KA, Grimm AA, Plueger MM, Bernal-Mizrachi E, Ford E, Cras-Méneur C, Permutt MA, and Imai S (2005) Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell Metab 2:105-117.
134. Murray-Zmijewski F, Slee EA, and Lu X (2008) A complex barcode underlies the heterogeneous response of p53 to stress. Nat Rev Mol Cell Biol 9:702-712.
135. Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D, Guarente LP, and Sassone-Corsi P (2008) The NAD-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134:329-340
136. Nakahata Y, Sahar S, Astarita G, Kaluzova M, and Sassone-Corsi P (2009) Circadian control of the NAD salvage pathway by CLOCK-SIRT1. Science 324:654-657
137. Nasrin N, Kaushik VK, Fortier E, Wall D, Pearson KJ, de Cabo R, and Bordone L (2009) JNK1 phosphorylates SIRT1 and promotes its enzymatic activity. PLoS One 4:e8414.
138. Neilson JR and Sharp PA (2008) Small RNA regulators of gene expression. Cell 134:899-902.
139. Nemoto S, Fergusson MM, and Finkel T (2004) Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science 306:2105-2108.
140. Nemoto S, Fergusson MM, and Finkel T (2005) SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. J Biol Chem 280:16456-16460.
141. Nisoli E, Clementi E, Paolucci C, Cozzi V, Tonello C, Sciorati C, Bracale R, Valerio A, Francolini M, Moncada S, et al. (2003) Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299:896-899.
142. Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, et al. (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314-317
143. North BJ, Marshall BL, Borra MT, Denu JM, and Verdin E (2003) The human Sir2 ortholog, SIRT2, is an NAD-dependent tubulin deacetylase. Mol Cell 11:437-444.
144. O'Reilly T and Niven DF (2003) Levels of nicotinamide adenine dinucleotide in extracellular body fluids of pigs may be growth-limiting for Actinobacillus pleuropneumoniae and Haemophilus parasuis. Can J Vet Res 67:229-231
145. Okazaki M, Iwasaki Y, Nishiyama M, Taguchi T, Tsugita M, Nakayama S, Kambayashi M, Hashimoto K, and Terada Y (2010) PPARbeta/delta regulates the human SIRT1 gene transcription via Sp1. Endocr J 57:403-413.
146. Onyango P, Celic I, McCaffery JM, Boeke JD, and Feinberg AP (2002) SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc Natl Acad Sci USA 99:13653-13658.
147. Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, Griffith D, Griffor M, Loulakis P, Pabst B, et al. (2010) SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 285: 8340-8351.
148. Park CE, Kim MJ, Lee JH, Min BI, Bae H, Choe W, Kim SS, and Ha J (2007) Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMPactivated protein kinase. Exp Mol Med 39:222-229.
149. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, et al. (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8:157-168.
150. Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, et al. (2011) The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics http://dx.doi.org/10.1074/mcp.M111.012658
151. Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, and Tschop MH (2008) Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci USA 105:9793-9798.
152. Philp A, Chen A, Lan D, Meyer GA, Murphy AN, Knapp AE, Olfert IM, McCurdy CE, Marcotte GR, Hogan MC, et al. (2011) Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation following endurance exercise. J Biol Chem 286:30561-30570.
153. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, and Guarente L (2004) Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 429:771-776
154. Pillai JB, Isbatan A, Imai S, and Gupta MP (2005) Poly(ADP-ribose) polymerase-1dependent cardiac myocyte cell death during heart failure is mediated by NAD depletion and reduced Sir2alpha deacetylase activity. J Biol Chem 280:43121-43130.
155. Pittelli M, Formentini L, Faraco G, Lapucci A, Rapizzi E, Cialdai F, Romano G, Moneti G, Moroni F, and Chiarugi A (2010) Inhibition of nicotinamide phosphoribosyltransferase: cellular bioenergetics reveals a mitochondrial insensitive NAD pool. J Biol Chem 285:34106-34114.
156. Ponugoti B, Kim DH, Xiao Z, Smith Z, Miao J, Zang M, Wu SY, Chiang CM, Veenstra TD, and Kemper JK (2010) SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. J Biol Chem 285:33959-33970
157. Puigserver P, Wu Z, Park CW, Graves R, Wright M, and Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829-839.
158. Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, and Li X (2009) Hepatocyte specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab 9:327-338.
159. Qiang L, Banks AS, and Accili D (2010) Uncoupling of acetylation from phosphory lation regulates FoxO1 function independent of its subcellular localization. J Biol Chem 285:27396-27401.
160. Ramsey KM, Mills KF, Satoh A, and Imai S (2008) Age-associated loss of Sirt1 mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice. Aging Cell 7:78-88.
161. Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, Hong HK, Chong JL, Buhr ED, Lee C, et al. (2009) Circadian clock feedback cycle through NAMPT-mediated NAD biosynthesis. Science 324:651-654
162. Revollo JR, Grimm AA, and Imai S (2004) The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem 279:50754-50763.
163. Revollo JR, Korner A, Mills KF, Satoh A, Wang T, Garten A, Dasgupta B, Sasaki Y, Wolberger C, Townsend RR, et al. (2007) Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 6:363-375.
164. Rizki G, Iwata TN, Li J, Riedel CG, Picard CL, Jan M, Murphy CT, and Lee SS (2011) The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet 7:e1002235
165. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, and Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434:113-118.
166. Rodgers JT and Puigserver P (2007) Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proc Natl Acad Sci USA 104:12861-12866
167. Rogina B and Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 101:15998-16003
168. Rongvaux A, Galli M, Denanglaire S, Van Gool F, Drèze PL, Szpirer C, Bureau F, Andris F, and Leo O (2008) Nicotinamide phosphoribosyl transferase/pre-B cell colony-enhancing factor/visfatin is required for lymphocyte development and cellular resistance to genotoxic stress. J Immunol 181:4685-4695.
169. Rutanen J, Yaluri N, Modi S, Pihlajamaki J, Vanttinen M, Itkonen P, Kainulainen S, Yamamoto H, Lagouge M, Sinclair DA, et al. (2010) SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity. Diabetes 59: 829-835.
170. Sahin E, Colla S, Liesa M, Moslehi J, Muller FL, Guo M, Cooper M, Kotton D, Fabian AJ, Walkey C, et al. (2011) Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 470:359-365.
171. Sakamoto J, Miura T, Shimamoto K, and Horio Y (2004) Predominant expression of Sir2alpha, an NAD-dependent histone deacetylase, in the embryonic mouse heart and brain. FEBS Lett 556:281-286.
172. Saleem A, Adhihetty PJ, and Hood DA (2009) Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle. Physiol Genomics 37:58-66.
173. Sasaki T, Maier B, Koclega KD, Chruszcz M, Gluba W, Stukenberg PT, Minor W, and Scrable H (2008) Phosphorylation regulates SIRT1 function. PLoS One 3:e4020
174. Satoh A, Brace CS, Ben-Josef G, West T, Wozniak DF, Holtzman DM, Herzog ED, and Imai S (2010) SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus. J Neurosci 30:10220-10232.
175. Sauve AA (2008) NAD and vitamin B3: from metabolism to therapies. J Pharmacol Exp Ther 324:883-893.
176. Sauve AA and Schramm VL (2002) Mechanism-based inhibitors of CD38: a mam malian cyclic ADP-ribose synthetase. Biochemistry 41:8455-8463.
177. Sauve AA, Wolberger C, Schramm VL, and Boeke JD (2006) The biochemistry of sirtuins. Annu Rev Biochem 75:435-465.
178. Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR, 3rd, et al. (2004) The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 119:61-74
179. Schmidt MT, Smith BC, Jackson MD, and Denu JM (2004) Coenzyme specificity of Sir2 protein deacetylases: implications for physiological regulation. J Biol Chem 279:40122-40129.
180. Schoonjans K, Staels B, and Auwerx J (1996) Role of the peroxisome proliferator activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 37:907-925.
181. Schwer B, North BJ, Frye RA, Ott M, and Verdin E (2002) The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase. J Cell Biol 158:647-657
182. Schwer B and Verdin E (2008) Conserved metabolic regulatory functions of sirtuins. Cell Metab 7:104-112.
183. Shi T, Wang F, Stieren E, and Tong Q (2005) SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem 280:13560-13567.
184. Shieh WM, Amé JC, Wilson MV, Wang ZQ, Koh DW, Jacobson MK, and Jacobson EL (1998) Poly(ADP-ribose) polymerase null mouse cells synthesize ADP-ribose polymers. J Biol Chem 273:30069-30072.
185. Shore D, Squire M, and Nasmyth KA (1984) Characterization of two genes required for the position-effect control of yeast mating-type genes. EMBO J 3:2817-2823
186. Sinclair DA and Guarente L (1997) Extrachromosomal rDNA circles-a cause of aging in yeast. Cell 91:1033-1042.
187. Skidmore CJ, Davies MI, Goodwin PM, Halldorsson H, Lewis PJ, Shall S, and Zia'ee AA (1979) The involvement of poly(ADP-ribose) polymerase in the degradation of NAD caused by gamma-radiation and N-methyl-N-nitrosourea. Eur J Biochem 101:135-142.
188. Strum JC, Johnson JH, Ward J, Xie H, Feild J, Hester A, Alford A, and Waters KM (2009) MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1. Mol Endocrinol 23:1876-1884.
189. Suchankova G, Nelson LE, Gerhart-Hines Z, Kelly M, Gauthier MS, Saha AK, Ido Y, Puigserver P, and Ruderman NB (2009) Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells. Biochem Biophys Res Commun 378:836-841.
190. Suwa M, Nakano H, Radak Z, and Kumagai S (2011) Short-term adenosine mono phosphate-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1beta-D-ribofuranoside treatment increases the sirtuin 1 protein expression in skeletal muscle. Metabolism 60:394-403.
191. Tanno M, Sakamoto J, Miura T, Shimamoto K, and Horio Y (2007) Nucleocytoplas mic shuttling of the NAD-dependent histone deacetylase SIRT1. J Biol Chem 282:6823-6832.
192. Timmers S, Konings E, Bilet L, Houtkooper RH, Weijer T, Goossens GH, Hoeks J, Krieken S, Ryu D, Kersten S, et al. (2011) Calorie-restriction-like effects of 30 days of resveratrol (resVidaTM) supplementation on energy metabolism and metabolic profile in obese humans. Cell Metabolism 14:612-622.
193. Tissenbaum HA and Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227-230.
194. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, and Offermanns S (2003) PUMA-G and HM74 are receptors for nicotinic acid and mediate its antilipolytic effect. Nat Med 9:352-355.
195. Um JH, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, Kim MK, Viollet B, and Chung JH (2010) AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 59:554-563.
196. Vaccari CS, Nagamia S, Thoenes M, Oguchi A, Hammoud R, and Khan BV (2007) Efficacy of controlled-release niacin in treatment of metabolic syndrome: Correlation to surrogate markers of atherosclerosis, vascular reactivity, and inflammation. J Clin Lipidol 1:605-613.
197. Vakhrusheva O, Braeuer D, Liu Z, Braun T, and Bober E (2008) Sirt7-dependent inhibition of cell growth and proliferation might be instrumental to mediate tissue integrity during aging. J Physiol Pharmacol 59:201-212.
198. Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, and Cellerino A (2006) Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 16:296-300.
199. van der Veer E, Ho C, O'Neil C, Barbosa N, Scott R, Cregan SP, and Pickering JG (2007) Extension of human cell lifespan by nicotinamide phosphoribosyltransferase. J Biol Chem 282:10841-10845.
200. van der Veer E, Nong Z, O'Neil C, Urquhart B, Freeman D, and Pickering JG (2005) Pre-B-cell colony-enhancing factor regulates NAD-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation. Circ Res 97:25-34.
201. van Roermund CW, Elgersma Y, Singh N, Wanders RJ, and Tabak HF (1995) The membrane of peroxisomes in Saccharomyces cerevisiae is impermeable to NAD(H) and acetyl-CoA under in vivo conditions. EMBO J 14:3480-3486
202. Vaquero A, Scher MB, Lee DH, Sutton A, Cheng HL, Alt FW, Serrano L, Sternglanz R, and Reinberg D (2006) SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev 20:1256-1261.
203. Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, and Weinberg RA (2001) hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107:149-159.
204. Viswanathan M and Guarente L (2011) Regulation of Caenorhabditis elegans lifes pan by sir-2.1 transgenes. Nature 477:E1-E2.
205. Viswanathan M, Kim SK, Berdichevsky A, and Guarente L (2005) A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell 9:605-615.
206. Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, Boss O, Hirsch ML, Ribich S, Smith JJ, et al. (2010) Conserved role of SIRT1 orthologs in fastingdependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev 24:1403-1417.
207. Wang RH, Li C, and Deng CX (2010) Liver steatosis and increased ChREBP expres sion in mice carrying a liver specific SIRT1 null mutation under a normal feeding condition. Int J Biol Sci 6:682-690.
208. Westphal S, Borucki K, Taneva E, Makarova R, and Luley C (2007) Extended-release niacin raises adiponectin and leptin. Atherosclerosis 193:361-365.
209. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, and Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686-689.
210. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, et al. (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115-124.
211. Xiong S, Salazar G, Patrushev N, and Alexander RW (2011) FoxO1 mediates an autofeedback loop regulating SIRT1 expression. J Biol Chem 286:5289-5299.
212. Xu F, Gao Z, Zhang J, Rivera CA, Yin J, Weng J, and Ye J (2010) Lack of SIRT1 (mammalian sirtuin 1) activity leads to liver steatosis in the SIRT1 / mice: a role of lipid mobilization and inflammation. Endocrinology 151:2504-2514.
213. Yamakuchi M, Ferlito M, and Lowenstein CJ (2008) miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA 105:13421-13426
214. Yamakuchi M and Lowenstein CJ (2009) MiR-34, SIRT1 and p53: the feedback loop. Cell Cycle 8:712-715.
215. Yamamoto H, Schoonjans K, and Auwerx J (2007) Sirtuin functions in health and disease. Mol Endocrinol 21:1745-1755.
216. Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, Lamming DW, Souza Pinto NC, Bohr VA, Rosenzweig A, et al. (2007a) Nutrient-sensitive mitochondrial NAD levels dictate cell survival. Cell 130:1095-1107.
217. Yang T, Chan NY, and Sauve AA (2007b) Syntheses of nicotinamide riboside and derivatives: effective agents for increasing nicotinamide adenine dinucleotide concentrations in mammalian cells. J Med Chem 50:6458-6461.
218. Yang T and Sauve AA (2006) NAD metabolism and sirtuins: metabolic regulation of protein deacetylation in stress and toxicity. AAPS J 8:E632-E643.
219. Yang Y, Fu W, Chen J, Olashaw N, Zhang X, Nicosia SV, Bhalla K, and Bai W (2007c) SIRT1 sumoylation regulates its deacetylase activity and cellular response to genotoxic stress. Nat Cell Biol 9:1253-1262.
220. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, and Mayo MW (2004) Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23:2369-2380.
221. Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, et al. (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131-138.
222. Yoshizaki T, Milne JC, Imamura T, Schenk S, Sonoda N, Babendure JL, Lu JC, Smith JJ, Jirousek MR, and Olefsky JM (2009) SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. Mol Cell Biol 29:1363-1374
223. Yoshizaki T, Schenk S, Imamura T, Babendure JL, Sonoda N, Bae EJ, Oh DY, Lu M, Milne JC, Westphal C, et al. (2010) SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. Am J Physiol Endocrinol Metab 298:E419-E428.
224. Yuan F, Xie Q, Wu J, Bai Y, Mao B, Dong Y, Bi W, Ji G, Tao W, Wang Y, et al. (2011a) MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation. J Biol Chem 286:6940-6945.
225. Yuan Y, Liao YM, Hsueh CT, and Mirshahidi HR (2011b) Novel targeted therapeu tics: inhibitors of MDM2, ALK and PARP. J Hematol Oncol 4:16.
226. Zang M, Xu S, Maitland-Toolan KA, Zuccollo A, Hou X, Jiang B, Wierzbicki M, Verbeuren TJ, and Cohen RA (2006) Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 55:2180-2191.
227. Zhang CY, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, Hagen T, Vidal-Puig AJ, Boss O, Kim YB, et al. (2001) Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105:745-755.
228. Zhang Q, Piston DW, and Goodman RH (2002) Regulation of corepressor function by nuclear NADH. Science 295:1895-1897.
229. Zhang Q, Wang SY, Fleuriel C, Leprince D, Rocheleau JV, Piston DW, and Goodman RH (2007) Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex. Proc Natl Acad Sci USA 104:829-833.
230. Zhao W, Kruse JP, Tang Y, Jung SY, Qin J, and Gu W (2008) Negative regulation of the deacetylase SIRT1 by DBC1. Nature 451:587-590.
231. Zhou S, Kachhap S, and Singh KK (2003) Mitochondrial impairment in p53-deficient human cancer cells. Mutagenesis 18:287-292.
232. Zini R, Morin C, Bertelli A, Bertelli AA, and Tillement JP (1999) Effects of resvera trol on the rat brain respiratory chain. Drugs Exp Clin Res 25:87-97.
233. Zschoernig B and Mahlknecht U (2009) Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2. Biochem Biophys Res Commun 381:372-377
234. Zwilling D, Huang SY, Sathyasaikumar KV, Notarangelo FM, Guidetti P, Wu HQ, Lee J, Truong J, Andrews-Zwilling Y, Hsieh EW, et al. (2011) Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell 145:863-874