Metabolic and neuropsychiatric effects of calorie restriction and sirtuins

Annual Review of Physiology

Volumn 75, Issue , 2013, Pages 669-684

  Libert, Sergiy ^a   Guarente, Leonard ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Longevity; SIRT1; Sirtuins

Indexed keywords

SIRTUIN; SIRTUIN 1; SIRTUIN 3; SIRTUIN 4; SIRTUIN 5; SIRTUIN 6; SIRTUIN 7;

AGING; BEHAVIOR; CALORIC RESTRICTION; CYTOPLASM; ENVIRONMENTAL FACTOR; HEALTH; HEREDITY; HUMAN; LIFESPAN; METABOLISM; MITOCHONDRION; MOOD; NONHUMAN; NUTRIENT; PRIORITY JOURNAL; PROTEIN FUNCTION; QUALITY OF LIFE; REVIEW;

AGING; ANIMALS; BEHAVIOR; BEHAVIOR, ANIMAL; BRAIN; CALORIC RESTRICTION; HUMANS; LONGEVITY; METABOLISM; MODELS, ANIMAL; SIRTUINS;

EID: 84873686589     PISSN: 00664278     EISSN: 15451585     Source Type: Book Series    
DOI: 10.1146/annurev-physiol-030212-183800     Document Type: Review

References (122)

1. McCay CM, Crowell MF, Maynard LA. 1935. The effect of retarded growth upon the length of life span and upon the ultimate body size. Nutrition 5:155-71; discussion 72
2. Guarente L. 2005. Calorie restriction and SIR2 genes-towards a mechanism. Mech. Ageing Dev. 126:923-28
3. Houthoofd K, Vanfleteren JR. 2006. The longevity effect of dietary restriction in Caenorhabditis elegans. Exp. Gerontol. 41:1026-31
4. Partridge L, Piper MD, Mair W. 2005. Dietary restriction in Drosophila. Mech. Ageing Dev. 126:938-50
5. Jones W. 1884. Longevity in a fasting spider. Science 3:4
6. Austad SN. 1989. Life extension by dietary restriction in the bowl and doily spider, Frontinella pyramitela. Exp. Gerontol. 24:83-92
7. Piper MD, Bartke A. 2008. Diet and aging. Cell Metab. 8:99-104
8. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, et al. 2009. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325:201-4
9. Libert S, Pletcher SD. 2007. Modulation of longevity by environmental sensing. Cell 131:1231-34
10. Wu P, Shen Q, Dong S, Xu Z, Tsien JZ, Hu Y. 2008. Calorie restriction ameliorates neurodegenerative phenotypes in forebrain-specific presenilin-1 and presenilin-2 double knockout mice. Neurobiol. Aging 29:1502-11
11. Weiss EP, Fontana L. 2011. Caloric restriction: powerful protection for the aging heart and vasculature. Am. J. Physiol. Heart Circ. Physiol. 301:H1205-19
12. Redman LM, Ravussin E. 2011. Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes. Antioxid. Redox Signal. 14:275-87
13. Sanders BD, Jackson B, Marmorstein R. 2010. Structural basis for sirtuin function: what we know and what we don't. Biochim. Biophys. Acta 1804:1604-16
14. North BJ, Schwer B, Ahuja N, Marshall B, Verdin E. 2005. Preparation of enzymatically active recom-binant class III protein deacetylases. Methods 36:338-45
15. Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, et al. 2006. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic βcells. Cell 126:941-54
16. Du J, Zhou Y, Su X, Yu JJ, Khan S, et al. 2011. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334:806-9
17. Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, et al. 2011. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell. Proteomics 10:M111. 012658
18. Bross TG, Rogina B, Helfand SL. 2005. Behavioral, physical, and demographic changes in Drosophila populations through dietary restriction. Aging Cell 4:309-17
19. Pletcher SD, Libert S, Skorupa D. 2005. Flies and their golden apples: the effect of dietary restriction on Drosophila aging and age-dependent gene expression. Ageing Res. Rev. 4:451-80
20. Walker G, Houthoofd K, Vanfleteren JR, Gems D. 2005. Dietary restriction in C. elegans: from rate-of-living effects to nutrient sensing pathways. Mech. Ageing Dev. 126:929-37
21. Rocha JS, Bonkowski MS, de Franca LR, Bartke A. 2007. Effects of mild calorie restriction on reproduction, plasma parameters and hepatic gene expression in mice with altered GH/IGF-I axis. Mech. Ageing Dev. 128:317-31
22. Bates GW, Bates SR, Whitworth NS. 1982. Reproductive failure in women who practice weight control. Fertil. Steril. 37:373-78
23. McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, et al. 2003. The mammalian SIR2α protein has a role in embryogenesis and gametogenesis. Mol. Cell. Biol. 23:38-54
24. Drenos F, Kirkwood TB. 2005. Modelling the disposable soma theory of ageing. Mech. Ageing Dev. 126:99-103
25. Walford RL, Spindler SR. 1997. The response to calorie restriction in mammals shows features also common to hibernation: a cross-adaptation hypothesis. J. Gerontol. A 52:B179-83
26. Weindruch R, Walford RL, Fligiel S, Guthrie D. 1986. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J. Nutr. 116:641-54
27. Lane MA, Baer DJ, Rumpler WV, Weindruch R, Ingram DK, et al. 1996. Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents. Proc. Natl. Acad. Sci. USA 93:4159-64
28. Soare A, Cangemi R, Omodei D, Holloszy JO, Fontana L. 2011. Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans. Aging 3:374-79
29. Lamb MJ. 1968. Temperature and lifespan in Drosophila. Nature 220:808-9
30. Conti B, Sanchez-Alavez M, Winsky-Sommerer R, Morale MC, Lucero J, et al. 2006. Transgenic mice with a reduced core body temperature have an increased life span. Science 314:825-28
31. Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, et al. 2007. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol. 27:8807-14
32. Shi T, Wang F, Stieren E, Tong Q. 2005. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J. Biol. Chem. 280:13560-67
33. Hirschey MD, Shimazu T, Huang JY, Schwer B, Verdin E. 2011. SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism. Cold Spring Harb. Symp. Quant. Biol. 76:267-77
34. Bell EL, Guarente L. 2011. The SirT3 divining rod points to oxidative stress. Mol. Cell 42:561-68
35. Someya S, Yu W, Hallows WC, Xu J, Vann JM, et al. 2010. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143:802-12
36. Sarkar RN, Das S. 1990. Effect of calorie restriction on the development of virus induced leukaemia in mice. Proc. Soc. Exp. Biol. Med. 193:164-66
37. Klurfeld DM, Weber MM, Kritchevsky D. 1987. Inhibition of chemically induced mammary and colon tumor promotion by caloric restriction in rats fed increased dietary fat. Cancer Res. 47:2759-62
38. Kritchevsky D. 2001. Caloric restriction and cancer. J. Nutr. Sci. Vitaminol. 47:13-19
39. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, et al. 2004. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305:390-92
40. Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, et al. 2001. hSIR2 functions as an NAD-dependent p53 deacetylase. Cell 107:149-59
41. Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, et al. 2008. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS ONE 3:e2020
42. Cho IR, Koh SS, Malilas W, Srisuttee R, Moon J, et al. 2012. SIRT1 inhibits proliferation of pancreatic cancer cells expressing pancreatic adenocarcinoma up-regulated factor (PAUF), a novel oncogene, by suppression of β3-catenin. Biochem. Biophys. Res. Commun. 423:270-75
43. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, et al. 2004. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-y. Nature 429:771-76
44. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. 2005. Nutrient control of glucose homeostasis through a complex of PGC-1txand SIRT1. Nature 434:113-18
45. Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, et al. 2005. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314-17
46. Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. 2009. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 9:327-38
47. Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, et al. 2008. A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 456:269-73
48. Noriega LG, Feige JN, Canto C, Yamamoto H, Yu J, et al. 2011. CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability. EMBO Rep. 12:1069-76
49. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, et al. 2004. Modulation of NF-xB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23:2369-80
50. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, et al. 2009. SIRT6 links histone H3 lysine 9 deacetylation to NF-xB-dependent gene expression and organismal life span. Cell 136:62-74
51. Kim HS, Xiao C, Wang RH, Lahusen T, Xu X, et al. 2010. Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metab. 12:224-36
52. Hallows WC, Yu W, Smith BC, Devries MK, Ellinger JJ, et al. 2011. Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction. Mol. Cell 41:139-49
53. Nakagawa T, Lomb DJ, Haigis MC, Guarente L. 2009. SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137:560-70
54. Shimazu T, Hirschey MD, Hua L, Dittenhafer-Reed KE, Schwer B, et al. 2010. SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production. Cell Metab. 12:654-61
55. Hallows WC, Lee S, Denu JM. 2006. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc. Natl. Acad. Sci. USA 103:10230-35
56. Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, et al. 2010. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464:121-25
57. Qiu X, Brown K, Hirschey MD, Verdin E, Chen D. 2010. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab. 12:662-67
58. Tao R, Coleman MC, Pennington JD, Ozden O, Park SH, et al. 2010. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol. Cell 40:893-904
59. Ahn BH, Kim HS, Song S, Lee IH, Liu J, et al. 2008. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc. Natl. Acad. Sci. USA 105:14447-52
60. Jing E, Emanuelli B, Hirschey MD, Boucher J, Lee KY, et al. 2011. Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. Proc. Natl. Acad. Sci. USA 108:14608-13
61. Nasrin N, Wu X, Fortier E, Feng Y, Bare OC, et al. 2010. SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells. J. Biol. Chem. 285:31995-2002
62. Ahuja N, Schwer B, Carobbio S, Waltregny D, North BJ, et al. 2007. Regulation of insulin secretion by SIRT4, a mitochondrial ADP- ribosyltransferase. J. Biol. Chem. 282:33583-92
63. Guarente L. 2011. Sirtuins, aging, and metabolism. Cold Spring Harb. Symp. Quant. Biol. 76:81-90
64. Chen D, Steele AD, Lindquist S, Guarente L. 2005. Increase in activity during calorie restriction requires Sirt1. Science 310:1641
65. Haigis MC, Sinclair DA. 2010. Mammalian sirtuins: biological insights and disease relevance. Annu. Rev. Pathol. Mech. Dis. 5:253-95
66. Xiong S, Salazar G, Patrushev N, Alexander RW. 2011. FoxO1 mediates an autofeedback loop regulating SIRT1 expression. J. Biol. Chem. 286:5289-99
67. Chen D, Bruno J, Easlon E, Lin SJ, Cheng HL, et al. 2008. Tissue-specific regulation of SIRT1 by calorie restriction. Genes Dev. 22:1753-57
68. Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, et al. 2007. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6:759-67
69. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, et al. 2007. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450:712-16
70. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, et al. 2006. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 127:1109-22
71. Banks AS, Kon N, Knight C, Matsumoto M, Gutierrez-Juarez R, et al. 2008. SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Cell Metab. 8:333-41
72. Donmez G, Wang D, Cohen DE, Guarente L. 2010. SIRT1 suppresses β-amyloid production by activating the α-secretase gene ADAM10. Cell 142:320-32
73. Jeong H, Cohen DE, Cui L, Supinski A, Savas JN, et al. 2012. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat. Med. 18:159-65
74. Donmez G, Arun A, Chung CY, McLean PJ, Lindquist S, Guarente L. 2012. SIRT1 protects against α-synuclein aggregation by activating molecular chaperones. J. Neurosci. 32:124-32
75. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, et al. 2007. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J. 26:3169-79
76. Gao J, Wang WY, Mao YW, Graff J, Guan JS, et al. 2010. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 466:1105-9
77. Westerheide SD, Anckar J, Stevens SM Jr, Sistonen L, Morimoto RI. 2009. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 323:1063-66
78. Liszt G, Ford E, Kurtev M, Guarente L. 2005. Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J. Biol. Chem. 280:21313-20
79. Michishita E, McCord RA, Berber E, Kioi M, Padilla-Nash H, et al. 2008. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452:492-96
80. Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, et al. 2006. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124:315-29
81. Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE, et al. 2010. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1α. Cell 140:280-93
82. Kaidi A, Weinert BT, Choudhary C, Jackson SP. 2010. Human SIRT6 promotes DNA end resection through CtIP deacetylation. Science 329:1348-53
83. Tennen RI, Bua DJ, Wright WE, Chua KF. 2011. SIRT6 is required for maintenance of telomere position effect in human cells. Nat. Commun. 2:433
84. Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, et al. 2012. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483:218-21
85. Michan S, Li Y, Chou MM, Parrella E, Ge H, et al. 2010. SIRT1 is essential for normal cognitive function and synaptic plasticity. J. Neurosci. 30:9695-707
86. +-dependent deacety-lase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134:329-40
87. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, et al. 2008. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134:317-28
88. Renthal W, Kumar A, Xiao G, Wilkinson M, Covington HE 3rd, et al. 2009. Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins. Neuron 62:335-48
89. Vitousek KM, Manke FP, Gray JA, Vitousek MN. 2004. Caloric restriction for longevity. II. The systematic neglect of behavioural and psychological outcomes in animal research. Eur. Eat. Disord. Rev. 12:338-60
90. Ramsey JJ, Colman RJ, Binkley NC, Christensen JD, Gresl TA, et al. 2000. Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study. Exp. Gerontol. 35:1131-49
91. Holtkamp K, Hebebrand J, Herpertz-Dahlmann B. 2004. The contribution of anxiety and food restriction on physical activity levels in acute anorexia nervosa. Int. J. Eat. Disord. 36:163-71
92. Levay EA, Paolini AG, Govic A, Hazi A, Penman J, Kent S. 2008. Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction. Behav. Brain Res. 191:164-72
93. Jahng JW, Kim JG, Kim HJ, Kim BT, Kang DW, Lee JH. 2007. Chronic food restriction in young rats results in depression-and anxiety-like behaviors with decreased expression of serotonin reuptake transporter. Brain Res. 1150:100-7
94. Jeninga EH, Schoonjans K, Auwerx J. 2010. Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility. Oncogene 29:4617-24
95. Kishi T, Yoshimura R, Kitajima T, Okochi T, Okumura T, et al. 2010. SIRT1 gene is associated with major depressive disorder in the Japanese population. J. Affect. Disord. 126:167-73
96. Libert S, Pointer K, Bell EL, Das A, Cohen DE, et al. 2011. SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive. Cell 147:1459-72
97. Smink FR, van Hoeken D, Hoek HW. 2012. Epidemiology of eating disorders: incidence, prevalence and mortality rates. Curr. Psychiatry Rep. 14:406-14
98. D'Andrea G, Ostuzzi R, Bolner A, Colavito D, Leon A. 2012. Is migraine a risk factor for the occurrence of eating disorders? Prevalence and biochemical evidences. Neurol. Sci. 33(Suppl. 1):71-76
99. Misra M, Aggarwal A, Miller KK, Almazan C, Worley M, et al. 2004. Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone density parameters in community-dwelling adolescent girls. Pediatrics 114:1574-83
100. Kumar RA, Marshall CR, Badner JA, Babatz TD, Mukamel Z, et al. 2009. Association and mutation analyses of 16p11. 2 autism candidate genes. PLoS ONE 4:e4582
101. Lecavalier L. 2006. Behavioral and emotional problems in young people with pervasive developmental disorders: relative prevalence, effects of subject characteristics, and empirical classification. J. Autism Dev. Disord. 36:1101-14
102. Krakowiak P, Walker CK, Bremer AA, Baker AS, Ozonoff S, et al. 2012. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 129:e1121-28
103. Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, et al. 2007. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat. Genet. 39:319-28
104. Sinclair DA, Guarente L. 1997. Extrachromosomal rDNA circles-a cause of aging in yeast. Cell 91:1033-42
105. Paffenbarger RS Jr, Hyde RT, Hsieh CC, Wing AL. 1986. Physical activity, other life-style patterns, cardiovascular disease and longevity. Acta Med. Scand. Suppl. 711:85-91
106. Sun D, Muthukumar AR, Lawrence RA, Fernandes G. 2001. Effects of calorie restriction on polymi-crobial peritonitis induced by cecum ligation and puncture in young C57BL/6 mice. Clin. Diagn. Lab. Immunol. 8:1003-11
107. Kristan DM. 2007. Chronic calorie restriction increases susceptibility of laboratory mice (Mus musculus) to a primary intestinal parasite infection. Aging Cell 6:817-25
108. Shanley DP, Kirkwood TB. 2006. Caloric restriction does not enhance longevity in all species and is unlikely to do so in humans. Biogerontology 7:165-68
109. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. 2008. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 7:681-87
110. Speakman JR, Mitchell SE. 2011. Caloric restriction. Mol. Aspects Med. 32:159-221
111. Villareal DT, Kotyk JJ, Armamento-Villareal RC, Kenguva V, Seaman P, et al. 2011. Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition. Aging Cell 10:96-102
112. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, et al. 2003. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191-96
113. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, et al. 2006. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337-42
114. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, et al. 1997. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218-20
115. Baur JA, Sinclair DA. 2006. Therapeutic potential of resveratrol: the in vivo evidence. Nat. Rev. Drug Discov. 5:493-506
116. Richard T, Pawlus AD, Iglesias ML, Pedrot E, Waffo-Teguo P, et al. 2011. Neuroprotective properties of resveratrol and derivatives. Ann. NY Acad. Sci. 1215:103-8
117. Dai H, Kustigian L, Carney D, Case A, Considine T, et al. 2010. SIRT1 activation by small molecules: kinetic and biophysical evidence for direct interaction of enzyme and activator. J. Biol. Chem. 285:32695-703
118. Park SJ, Ahmad F, Philp A, Baar K, Williams T, et al. 2012. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148:421-33
119. Bemis JE, Vu CB, Xie R, Nunes JJ, Ng PY, et al. 2009. Discovery of oxazolo[4, 5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators. Bioorg. Med. Chem. Lett. 19:2350-53
120. Vu CB, Bemis JE, Disch JS, Ng PY, Nunes JJ, et al. 2009. Discovery of imidazo[1, 2-b]thiazole derivatives as novel SIRT1 activators. J. Med. Chem. 52:1275-83
121. + precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 15:838-47
122. Revollo JR, Korner A, Mills KF, Satoh A, Wang T, et al. 2007. Nampt/PBEF/visfatin regulates insulin secretion in βcells as a systemic NAD biosynthetic enzyme. Cell Metab. 6:363-75