Glycolytic inhibition as a strategy for developing calorie restriction mimetics

Experimental Gerontology

Volumn 46, Issue 2-3, 2011, Pages 148-154

  Ingram, Donald K ^a   Roth, George S ^b  

^a PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

^b GeroScience Inc   (United States)

Author keywords

Calorie restriction; Diet restriction; Glucose; Hexokinase; Insulin; Metformin; MTOR; Resveratrol; Sirtuin

Indexed keywords

BROMOPYRUVIC ACID; DEOXYGLUCOSE; GLUCOSE REGULATED PROTEIN 78; HEAT SHOCK PROTEIN 70; INSULIN; LACTIC ACID DERIVATIVE; MAMMALIAN TARGET OF RAPAMYCIN; SIRTUIN; UNCLASSIFIED DRUG;

CALORIC RESTRICTION; CARDIOTOXICITY; ENERGY EXPENDITURE; FOOD INTAKE; GLYCOLYSIS; HUMAN; LONGEVITY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; RISK REDUCTION; SIGNAL TRANSDUCTION; STRESS;

AGING; ANIMALS; CALORIC RESTRICTION; GLYCOLYSIS; HUMANS; INSULIN; MODELS, ANIMAL; SIGNAL TRANSDUCTION; SIRTUINS; TOR SERINE-THREONINE KINASES;

RATTUS;

EID: 78751704506     PISSN: 05315565     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.exger.2010.12.001     Document Type: Review

References (112)

1. Aljada A., Dong L., Mousa S.A. Sirtuin-targeting drugs: mechanisms of action and potential therapeutic applications. Curr. Opin. Investig. Drugs 2010, 11:1158-1168.
2. Anisimov V.N. Insulin/IGF-1 signaling pathway driving aging and cancer as a target for pharmacological intervention. Exp. Gerontol. 2003, 38:1041-1049.
3. Anisimov V.N., Berstein L.M., Egormin P.A., Piskunova T.S., Popovich I.G., Zabezhinski M.A., Kovalenko I.G., Poroshina T.E., Semenchenko A.V., Provinciali M., Re F., Franceschi C. Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp. Gerontol. 2005, 40:685-693.
4. Anisimov V.N., Egormin P.A., Bershtein L.M., Zabezhinskii M.A., Piskunova T.S., Popovich I.G., Semenchenko A.V. Metformin decelerates aging and development of mammary tumors in HER-2/neu transgenic mice. Bull. Exp. Biol. Med. 2005, 139:721-723.
5. Anisimov V.N., Berstein L.M., Egormin P.A., Piskunova T.S., Popovich I.G., Zabezhinski M.A., Tyndyk M.L., Yurova M.V., Kovalenko I.G., Poroshina T.E., Semenchenko A.V. Metformin slows down aging and extends life span of female SHR mice. Cell Cycle 2008, 7:2769-2773.
6. Anisimov V.N., Egormin P.A., Piskunova T.S., Popovich I.G., Tyndyk M.L., Yurova M.N., Zabezhinski M.A., Anikin I.V., Karkach A.S., Romanyukha A.A. Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle 2010, 9:188-197.
7. Anisimov V.N., Zabezhinski M.A., Popovich I.G., Piskunova T.S., Semenchenko A.V., Tyndyk M.L., Yurova M.N., Antoch M.P., Blagosklonny M.V. Rapamycin extends maximal lifespan in cancer-prone mice. Am. J. Pathol. 2010, 176:2092-2097.
8. Bailey C.J., Turner R.C. Metformin. N. Engl. J. Med. 1996, 334:574-579.
9. Barger J.L., Kayo T., Vann J.M., Arias E.B., Wang J., Hacker T.A., Wang Y., Raederstorff D., Morrow J.D., Leeuwenburgh C., Allison D.B., Saupe K.W., Cartee G.D., Weindruch R., Prolla T.A. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE 2008, 3:e2264.
10. Bartke A. Insulin and aging. Cell Cycle 2008, 7:3338-3344.
11. Bass T.M., Weinkove D., Hourthoofd K., Gems D., Partridge L. Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech. Ageing Dev. 2007, 128:546-552.
12. Baur J.A. Resveratrol, sirtuins, and the promise of a DR mimetic. Mech. Ageing Dev. 2010, 131:261-269.
13. Baur J.A., Pearson K.J., Price N.L., Jamieson H.A., Lerin C., Kalra A., Prabhu V.V., Allard J.S., Lopez-Lluch G., Lewis K., Pistell P.J., Poosala S., Becker K.G., Boss O., Gwinn D., Wang M., Ramaswamy S., Fishbein K.W., Spencer R.G., Lakatta E.G., Le Couteur D., Shaw R.J., Navas P., Puigserver P., Ingram D.K., de Cabo R., Sinclair D.A. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006, 444:337-342.
14. Ben Sahra I., Le Marchand-Brustel Y., Tanti J.F., Bost F. Metformin in cancer therapy: a new perspective for an old antidiabetic drug?. Mol. Cancer Ther. 2010, 9:1092-1099.
15. Blagosklonny M.V. Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans). Cell Cycle 2010, 15:683-688.
16. Caccamo A., Majumder S., Richardson A., Strong R., Oddo S. Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J. Biol. Chem. 2010, 285:13107-13120.
17. Calabrese E.J. Hormesis: From marginalization to mainstream: a case for hormesis as the default dose-response model in risk assessment. Toxicol. Appl. Pharmacol. 2004, 197:125-136.
18. Chang J.M., Chung J.W., Jae H.J., Eh H., Son K.R., Lee K.C., Park J.H. Local toxicity of hepatic arterial infusion of hexokinase II inhibitor, 3-bromopyruvate: in vivo investigation in normal rabbit model. Acad. Radiol. 2007, 14:85-92.
19. Chao J., Yu M.S., Ho Y.S., Wang M., Chang R.C. Dietary oxyresveratrol prevents parkinsonian mimetic 6-hydroxydopamine neurotoxicity. Free Radic. Biol. Med. 2008, 45:1019-1026.
20. Chen D., Guarente L. SIR2: a potential target for calorie restriction mimetics. Trends Mol. Med. 2007, 13:64-71.
21. Ciuffreda L., Di Sanza C., Incani U.C., Milella M. The mTOR pathway: a new target in cancer therapy. Curr. Cancer Drug Targets 2010, 10:484-495.
22. Collier C.A., Bruce C.R., Smith A.C., Lopaschuk G., Dyck D.J. Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2006, 291:E182-E189.
23. Dai H., Kustigian L., Carney D., Case A., Considine T., Hubbard B.P., Perni R.B., Riera T.V., Szczepankiewicz B., Vlasuk G.P., Stein R.L. SIRT1 activation by small molecules-kinetic and biophysical evidence for direct interaction of enzyme and activator. J. Biol. Chem. 2010, 285(43):32695-32703.
24. Dark J., Miller D.R., Zucker I. Reduced glucose availability induces torpor in Siberian hamsters. Am. J. Physiol. 1994, 267:496-501.
25. Das D.K., Mukherjee S., Ray D. Resveratrol and red wine, healthy heart and longevity. Heart Fail. Rev. 2010, 15:467-477.
26. Davenport G., Massimino S., Hayek M., Burr J., Michael Ceddia M., Yeh C.-H., Roth G., Ingram D. Biological activity of avocado-derived mannoheptulose in dogs. Exp. Biol. Abstr. 2010, 725.4. http://www.fasebj.org/cgi/content/meeting_abstract/24/1_MeetingAbstracts/725.4.
27. Dhahbi J.M., Mote P.L., Fahy G.M., Spindler S.R. Identification of potential caloric restriction mimetics by microarray profiling. Physiol. Genomics 2005, 23:343-350.
28. Duan W., Mattson M.P. Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson's disease. J. Neurosci. Res. 1999, 57:195-206.
29. Eurich D.T., Majumdar S.R., McAlister F.A., Tsuyuki R.T., Johnson J.A. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diab. Care 2005, 28:2345-2351.
30. Feige J.N., Lagouge M., Canto C., Strehle A., Houten S.M., Milne J.C., Lambert P.D., Mataki C., Elliott P.J., Auwerx J. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab. 2008, 8:347-358.
31. Froelich L., Ding A., Hoyer S. Holeboard maze-learning deficits and brain monoaminergic neurotransmitter concentrations in rats after intracerebroventricular injection of 3-bromopyruvate. Pharmacol. Biochem. Behav. 1995, 51:917-922.
32. Fuemayor L.D., Diaz S. The effect of feeding on the stereotyped behaviour induced by amphetamine and by apomorphine in the albino rat. Eur. J. Pharmacol. 1984, 99:153-158.
33. Giovannucci E., Harlan D.M., Archer M.C., Bergenstal R.M., Gapstur S.M., Habel L.A., Pollak M., Regensteiner J.G., Yee D. Diabetes and cancer: a consensus report. CA Cancer J. Clin. 2010, 60:207-221.
34. Gresl T.A., Colman R.J., Roecker E.B., Havighurst T.C., Huang Z., Allison D.B., Bergman R.N., Kemnitz J.W. Dietary restriction and glucose regulation in aging rhesus monkeys: a follow-up report at 8.5 yr. Am. J. Physiol. Endocrinol. Metab. 2001, 281:E757-E765.
35. Gridley D.S., Nutter R.L., Kettering J.D., Mantik D.W., Slater J.M. Mouse neoplasia and immunity: effects of radiation, hyperthermia, 2-deoxy-d-glucose, and Corynebacterium parvum. Oncology 1985, 42:391-398.
36. Guo Z., Mattson M.P. In vivo 2-deoxyglucose administration preserves glucose and glutamate transport and mitochondrial function in cortical synaptic terminals after exposure to amyloid β-peptide and iron: evidence for a stress response. Exp. Neurol. 2000, 166:173-179.
37. Guo Z., Lee J., Lane M., Mattson M. Iodoacetate protects hippocampal neurons against excitotoxic and oxidative injury: involvement of heat-shock proteins and Bcl-2. J. Neurochem. 2001, 79:361-370.
38. Gupta Y.K., Briyal S., Chaudhary G. Protective effect of trans-resveratrol against kainic acid-induced seizures and oxidative stress in rats. Pharmacol. Biochem. Behav. 2002, 71:245-249.
39. Hands S.L., Proud C.G., Wyttenbach A. mTOR's role in ageing: protein synthesis or autophagy?. Aging 2009, 20:586-597.
40. Hansen B.C., Bodkin N.L., Ortmeyer H.K. Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality. Toxicol. Sci. 1999, 52:56-60.
41. Harrison D.E., Strong R., Sharp Z.D., Nelson J.F., Astle C.M., Flurkey K., Nadon N.L., Wilkinson J.E., Frenkel K., Carter C.S., Pahor M., Javors M.A., Fernandez E., Miller R.A. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009, 460:392-395.
42. Hay N., Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004, 18:1926-1945.
43. Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S., Wood J.G., Zipkin R.E., Chung P., Kisielewski A., Zhang L.L., Scherer B., Sinclair D.A. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003, 425:191-196.
44. http://www.thresholdpharm.com.
45. Ingram D.K., Zhu M., Mamczarz J., Zou S., Lane M.A., Roth G.S., de Cabo R. Calorie restriction mimetics: an emerging research field. Aging Cell 2006, 5:97-108.
46. Jones A.R., Porter K.E., Dobbie M.S. Renal and spermatozoal toxicity of alpha-bromohydrin, 3-bromolactate and 3-bromopyruvate. J. Appl. Toxicol. 1996, 16:57-63.
47. Kaeberlein M. Resveratrol and rapamycin: are they anti-aging drugs?. Bioessays 2010, 32:96-99.
48. Kang H.T., Hwang E.S. 2-Deoxyglucose: an anticancer and antiviral therapeutic, but not any more a low glucose mimetic. Life Sci. 2006, 78:1392-1399.
49. Kapahi P., Chen D., Rogers A.N., Katewa S.D., Li P.W., Thomas E.L., Kockel L. With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab. 2010, 11:453-465.
50. Karuppagounder S.S., Pinto J.T., Xu H., Chen H.L., Beal M.F., Gibson G.E. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease. Neurochem. Int. 2009, 54:111-118.
51. Khan M.M., Ahmad A., Ishrat T., Khan M.B., Hoda M.N., Khuwaja G., Raza S.S., Khan A., Javed H., Vaibhav K., Islam F. Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson's disease. Brain Res. 2010, 1328:139-151.
52. Kim Y.D., Park K.G., Lee Y.S., Kim D.K., Nedumaran B., Jang W.G., Cho W.J., Ha J., Lee I.K., Lee C.H., Choi H.S. Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes 2008, 57:306-314.
53. Kirpichnikov D., McFarlane S.I., Sowers J.R. Metformin: an update. Ann. Intern. Med. 2002, 137:25-33.
54. Ko Y.H., Pedersen P.L., Geschwind J.F. Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase. Cancer Lett. 2001, 173:83-91.
55. Ko Y.H., Smith B.L., Wang Y., Pomper M.G., Rini D.A., Torbenson M.S., Hullihen J., Pedersen P.L. Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochem. Biophys. Res. Commun. 2004, 324:269-275.
56. Kume S., Uzu T., Kashiwagi A., Koya D. SIRT1, a calorie restriction mimetic, in a new therapeutic approach for type 2 diabetes mellitus and diabetic vascular complications. Endocr. Metab. Immune Disord. Drug Targets 2010, 16-24.
57. Lane M.A., Ingram D.K., Roth G.S. 2-Deoxy-d-glucose feeding in rats mimics physiological effects of calorie restriction. J. Anti-Aging Med. 1998, 1:327-337.
58. Lane M.A., Ingram D.K., Roth G.S. Calorie restriction in nonhuman primates: effects on diabetes and cardiovascular disease risk. Toxicol. Sci. 1999, 52:41-48.
59. Lavu S., Boss O., Elliott P.J., Lambert P.D. Sirtuins-novel therapeutic targets to treat age-associated diseases. Nat. Rev. Drug Discov. 2008, 7:841-853.
60. Lee J., Bruce-Keller A.J., Kruman Y., Chan S.L., Mattson M.P. 2-Deoxy-d-glucose protects hippocampal neurons against excitotoxic and oxidative injury: evidence for the involvement of stress proteins. J. Neurosci. Res. 1999, 57:48-61.
61. Mamczarz J., Duffy K., Bowker J., Zhu M., Hagepanos A., Ingram D. Enhancement of amphetamine-induced locomotor response in rats on different regimens of diet restriction and 2-deoxyglucose treatment. Neuroscience 2005, 131:451-461.
62. Marwarha G., Dasari B., Prabhakara J.P., Schommer J., Ghribi O. beta-Amyloid regulates leptin expression and tau phosphorylation through the mTORC1 signaling pathway. J. Neurochem. 2010, 115(2):373-384.
63. Mattson M. Dietary factors, hormesis health. Ageing Res. Rev. 2008, 7:43-48.
64. Mattson M.P., Duan W., Lee J., Guo Z., Roth G.S., Ingram D.K., Lane M.A. Progress in the development of caloric restriction mimetic supplements. J. Anti-Aging Med. 2001, 4:225-232.
65. Merry B.J., Kirk A.J., Goyns M.H. Dietary lipoic acid supplementation can mimic or block the effect of dietary restriction on life span. Mech. Ageing Dev. 2008, 129:341-348.
66. Milne J.C., Lambert P.D., Schenk S., Carney D.P., Smith J.J., Gagne D.J., Jin L., Boss O., Perni R.B., Vu C.B., Bemis J.E., Xie R., Disch J.S., Ng P.Y., Nunes J.J., Lynch A.V., Yang H., Galonek H., Israelian K., Choy W., Iffland A., Lavu S., Medvedik O., Sinclair D.A., Olefsky J.M., Jirousek M.R., Elliott P.J., Westphal C.H. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 2007, 450:712-716.
67. Minor R.K., Smith D.L., Sossong A.M., Kaushik S., Poosala S., Spangler E.L., Roth G.S., Lane M., Allison D.B., de Cabo R., Ingram D.K., Mattison J.A. Chronic ingestion of 2-deoxy-d-glucose induces cardiac vacuolization and increases mortality in rats. Toxicol. Appl. Pharmacol. 2010, 243:332-339.
68. Onken B., Driscoll M. Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans healthspan via AMPK, LKB1, and SKN-1. PLoS ONE 2010, 5:e8758.
69. Pacholec M., Bleasdale J.E., Chrunyk B., Cunningham D., Flynn D., Garofalo R.S., Griffith D., Griffor M., Loulakis P., Pabst B., Qiu X., Stockman B., Thanabal V., Varghese A., Ward J., Withka J., Ahn K. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J. Biol. Chem. 2010, 285:8340-8351.
70. Papanas N., Maltezos E. Oral antidiabetic agents: anti-atherosclerotic properties beyond glucose lowering?. Curr. Pharm. Des. 2009, 15:3179-3192.
71. Parker J.C. Glucose-6-phosphate translocase as a target for the design of antidiabetic agents. Drugs Fut 2001, 26:687.
72. Pearson K.J., Baur J.A., Lewis K.N., Peshkin L., Price N.L., Labinskyy N., Swindell W.R., Kamara D., Minor R.K., Perez E., Jamieson H.A., Zhang Y., Dunn S.R., Sharma K., Pleshko N., Woollett L.A., Csiszar A., Ikeno Y., Le Couteur D., Elliott P.J., Becker K.G., Navas P., Ingram D.K., Wolf N.S., Ungvari Z., Sinclair D.A., de Cabo R. Resveratrol Delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008, 8:157-168.
73. Pedersen P.L. Warburg, me and hexokinase 2: multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen. J. Bioenerg. Biomembr. 2007, 39:211-219.
74. Pilmore H.L. Metformin: potential benefits and use in chronic kidney disease. Nephrology 2010, 15:412-418.
75. Rattan S.I.S. Hormesis in aging. Ageing Res. Rev. 2008, 7:63-78.
76. Roth G.S., Lane M.A., Ingram D.K., Mattison J., Elahi D., Tobin J., Muller D., Metter E.J. Biomarkers of caloric restriction may predict longevity in humans. Science 2002, 297:881.
77. Roth G.S., Lane M.A., Ingram D.K. Caloric restriction mimetics: the next phase. Ann. NY Acad. Sci. 2005, 1057:365-371.
78. Roth G., Hayek M., Massimino S., Davenport G., Arking R., Bartke A., Bonkowski M., Ingram D. Mannoheptulose: glycolytic inhibitor and novel caloric restriction mimetic. Exp. Biol. Abstr. 2009, 553.1. http://www.fasebj.org/cgi/content/meeting_abstract/23/1_MeetingAbstracts/553.1.
79. Sakata Y., Zhuang H., Kwansa H., Koehler R.C., Doré S. Resveratrol protects against experimental stroke: putative neuroprotective role of heme oxygenase 1. Exp. Neurol. 2010, 224:325-329.
80. Salminen A., Kaarniranta K. Regulation of the aging process by autophagy. Trends Mol. Med. 2009, 15:217-224.
81. Sarbassov Dos D., Sabatini David M. Redox regulation of the nutrient-sensitive raptor-mTOR pathway and complex. J. Biol. Chem. 2005, 280:39505-39509.
82. Scarpello J.H. Improving survival with metformin: the evidence base today. Diab. Metab. 2003, 29:6S36-6S43.
83. Schmidt C. GSK/Sirtris compounds dogged by assay artifacts. Nat. Biotechnol. 2010, 28:185-186.
84. Schulz T.J., Zarse K., Voigt A., Urban N., Birringer M., Ristow M. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 2007, 6:280-293.
85. Sinclair D.A. Toward a unified theory of caloric restriction and longevity regulation. Mech. Ageing Dev. 2005, 126:987-1002.
86. Smith J.J., Kenney R.D., Gagne D.J., Frushour B.P., Ladd W., Galonek H.L., Israelian K., Song J., Razvadauskaite G., Lynch A.V., Carney D.P., Johnson R.J., Lavu S., Iffland A., Elliott P.J., Lambert P.D., Elliston K.O., Jirousek M.R., Milne J.C., Boss O. Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo. BMC Syst. Biol. 2009, 10:31.
87. Smith D.L., Elam C.F., Mattison J.A., Lane M.A., Roth G.S., Ingram D.K., Allison D.B. Metformin supplementation and life span in Fischer-344 rats. J. Gerontol. A Biol. Sci. Med. Sci. 2010, 65:468-474.
88. Smith D.L., Nagy T.R., Wilson L.S., Dong S., Barnes S., Allison D.B. The effect of mannan oligosaccharide supplementation on body weight gain and fat accrual in C57Bl/6J mice. Obesity 2010, 18:995-999.
89. Sparks C.A., Guertin D.A. Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy. Oncogene 2010, 29:3733-3744.
90. Spilman P., Podlutskaya N., Hart M.J., Debnath J., Gorostiza O., Bredesen D., Richardson A., Strong R., Galvan V. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS ONE 2010, 5:e9979.
91. Stanfel M.N., Shamieh L.S., Kaeberlein M., Kennedy B.K. The TOR pathway comes of age. Biochim. Biophys. Acta 2009, 1790:1067-1074.
92. Swiech L., Perycz M., Malik A., Jaworski J. Role of mTOR in physiology and pathology of the nervous system. Biochim. Biophys. Acta 2008, 1784:116-132.
93. Tatar M., Bartke A., Antebi A. The endocrine regulation of aging by insulin-like signals. Science 2003, 299:1346-1355.
94. Tokunaga C., Yoshino K., Yonezawa K. mTOR integrates amino acid- and energy-sensing pathways. Biochem. Biophys. Res. Commun. 2004, 313:443-446.
95. Tzatsos A., Kandror K.V. Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol. Cell. Biol. 2006, 26:63-76.
96. Valenzano D.R., Terzibasi E., Genade T., Cattaneo A., Domenici L., Cellerino A. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr. Biol. 2006, 16:296-300.
97. Wan R., Camandola S., Mattson M.P. Intermittent fasting and dietary supplementation with 2-deoxy-d-glucose improve functional and metabolic cardiovascular risk factors in rats. FASEB J. 2003, 17:1133-1134.
98. Wan R., Camandola S., Mattson M.P. Dietary supplementation with 2-deoxy-d-glucose improves cardiovascular and neuroendocrine stress adaptation in rats. Am. J. Physiol. Heart Circ. Physiol. 2004, 287:H1186-H1193.
99. Wang Xuemin, Beugnet Anne, Murakami Mirei, Yamanaka Shinya, Proud Christopher G. Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins. Mol. Cell Biol. (United States) 2005, 25(7):2558-2572. April.
100. Warburg O., Posener K., Negelein E. Ueber den Stoffwechsel der Tumoren. Biochem. Z. 1930, 152:319-344.
101. Wei S., Kulp S.K., Chen C.S. Energy restriction as an antitumor target of thiazolidinediones. J. Biol. Chem. 2010, 2285:9780-9791.
102. Wood J.G., Rogina B., Lavu S., Howitz K., Helfand S.L., Tatar M., Sinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 2004, 430:686-689.
103. Wu Z., Xu Q., Zhang L., Kong D., Ma R., Wang L. Protective effect of resveratrol against kainate-induced temporal lobe epilepsy in rats. Neurochem. Res. 2009, 34:1393-1400.
104. Xu R.H., Pelicano H., Zhou Y., Carew J.S., Feng L., Bhalla K.N., Keating M.J., Huang P. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res. 2005, 65:613-621.
105. Yang Q., Inoki K., Ikenoue T., Guan K.L. Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev. 2006, 20:2820-2832.
106. Yang D.L., Zhang H.G., Xu Y.L., Gao Y.H., Yang X.J., Hao X.Q., Li X.H. Resveratrol inhibits right ventricular hypertrophy induced by monocrotaline in rats. Clin. Exp. Pharmacol. Physiol. 2010, 37:150-155.
107. Yousuf S., Atif F., Ahmad M., Hoda N., Ishrat T., Khan B., Islam F. Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia. Brain Res. 2009, 1250:242-253.
108. Yu Z.F., Mattson M.P. Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: evidence for a preconditioning mechanism. J. Neurosci. Res. 1999, 57:830-839.
109. Zemke D., Azhar S., Majid A. The mTOR pathway as a potential target for the development of therapies against neurological disease. Drug News Perspect. 2007, 20:495-499.
110. Zhang S., Salemi J., Hou H., Zhu Y., Mori T., Giunta B., Obregon D., Tan J. Rapamycin promotes beta-amyloid production via ADAM-10 inhibition. Biochem. Biophys. Res. Commun. 2010, 398:337-341.
111. Zhu Z., Jiang W., McGinley J.N., Thompson H.J. 2-Deoxyglucose as an energy restriction mimetic agent: effects on mammary carcinogenesis and on mammary tumor cell growth in vitro. Cancer Res. 2005, 65:7023-7030.
112. Zou S., Carey J.R., Liedo P., Ingram D.K., Müller H.G., Wang J.L., Yao F., Yu B., Zhou A. The prolongevity effect of resveratrol depends on dietary composition and calorie intake in a tephritid fruit fly. Exp. Gerontol. 2009, 44:472-476.