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Resveratrol and red wine, healthy heart and longevity

An Erratum to this article was published on 13 March 2011


Resveratrol, a polyphenol phytoalexin, present in red wine and grapes possesses diverse biochemical and physiological properties, including estrogenic, antiplatelet, and anti-inflammatory properties as well as a wide range of health benefits ranging from chemoprevention to cardioprotection. Recently, several studies described resveratrol as an anti-aging compound. This review focuses on the anti-aging aspects of resveratrol, the possible mechanisms of action, and emerging controversy on its life-prolonging ability. It appears that resveratrol can induce the expression of several longevity genes including Sirt1, Sirt3, Sirt4, FoxO1, Foxo3a and PBEF and prevent aging-related decline in cardiovascular function including cholesterol level and inflammatory response, but it is unable to affect actual survival or life span of mice.

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Fig. 1
Fig. 2





Forkhead transcription factor.


Pre B cell colony enhancing factor.


Low-density lipoprotein.


Basal metabolic rate.


Calorie restriction.


Insulin-dependent growth factor 1


Reactive oxygen species


Nitric oxide synthase


Vascular endothelial growth factor


Glucose transporter type 4


Polyunsaturated fatty acids


Heme oxygenase-1


Protein kinase C

PI3 kinase:





Prostaglandin E2


Tumor necrosis factor α


  1. 1.

    Bertelli AA, Das DK (2009) Grapes, wines, resveratrol and heart health. J Cardiovasc Pharmacol 54:468–476

    Google Scholar 

  2. 2.

    Kopp P (1998) Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the ‘French paradox’? Eur J Endocrinol 38(6):619–620

    Google Scholar 

  3. 3.

    Wang Z, Zou J, Cao K, Hsieh TC, Huang Y, Wu JM (2005) Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. Int J Mol Med. 16(4):533–540

    PubMed  CAS  Google Scholar 

  4. 4.

    Das DK, Sato M, Ray PS, Maulik G, Engelman RM, Bertelli AA, Bertelli A (1999) Drugs exp. Clin Res 25(2–3):115–120

    CAS  Google Scholar 

  5. 5.

    Castello L, Tessitore L (2005) Resveratrol inhibits cell cycle progression in U937 cells. Oncol Rep 13(1):133–137

    PubMed  CAS  Google Scholar 

  6. 6.

    Zhuang H, Kim YS, Koehler RC, Doré S (2003) Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann N Y Acad Sci 993:276–286 discussion 287–288

    PubMed  CAS  Google Scholar 

  7. 7.

    Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirutins extend Saccharomyces cerevisiae lifespan. Nature 425(6954):191–196

    PubMed  CAS  Google Scholar 

  8. 8.

    Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5(6):493–506

    PubMed  CAS  Google Scholar 

  9. 9.

    Mukherjee S, Lekli I, Gurusamy N, Bertelli AA, Das DK (2009) Expression of the longevity proteins by both red and white wines and their chemoprotective components, resveratrol, tyrosol, and hydroxytyrosol. Free Radic Biol Med 46(5):573–578

    PubMed  CAS  Google Scholar 

  10. 10.

    Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliot PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 8(2):157–168

    PubMed  CAS  Google Scholar 

  11. 11.

    Mittlemark BM, Rautaharju PM (1993) Prevalence of cardiovascular diseases among older adults. The Cardiovascular Health Study. Am J Epidemiol 137:311–334

    Google Scholar 

  12. 12.

    Rezzi S, Martin FP, Shanmuganayagam D, Colman RJ, Nicholson JK, Weindruch R (2009) Metabolic shifts due to long-term caloric restriction revealed in nonhuman primates. Exp Gerontol 44(5):356–362

    PubMed  CAS  Google Scholar 

  13. 13.

    Walford RL (1988) The retardation of aging and disease by dietary restriction. Richard Weindruch, ISBN 0-398-05496-7

  14. 14.

    Mattson MP (2005) Energy intake, meal frequency, and health: a neurobiological perspective. Ann Rev Nutr 25:237–260

    CAS  Google Scholar 

  15. 15.

    Richard JL (1987) Coronary risk factors. The French paradox. Arch Mal Coeur Vaiss 80 Spec No:17–21

  16. 16.

    Hattori R, Otani H, Maulik N, Das DK (2002) Pharmacological preconditioning with resveratrol: role of nitric oxide. Am J Physiol Heart Circ Physiol 282:H1988–H1995

    PubMed  CAS  Google Scholar 

  17. 17.

    Cadenas S, Barja G (1999) Resveratrol, melatonin, vitamin E, and PBN protect against renal oxidative DNA damage induced by the kidney carcinogen KBrO3. Free Radic Biol Med 26:1531–1537

    PubMed  CAS  Google Scholar 

  18. 18.

    Imamura G, Bertelli AA, Bertelli A, Otani H, Maulik N, Das DK (2002) Pharmacological preconditioning with resveratrol: an insight with iNOS knockout mice. Am J Physiol Heart Circ Physiol 282:H1996–H2003

    PubMed  CAS  Google Scholar 

  19. 19.

    Das S, Alagappan VK, Bagchi D, Sharma HS, Maulik N, Das DK (2005) Coordinated induction of iNOS-VEGF-KDR-eNOS after resveratrol consumption: a potential mechanism for resveratrol preconditioning of the heart. Vascul Pharmacol 42:281–289

    PubMed  CAS  Google Scholar 

  20. 20.

    Fukuda S, Kaga S, Zhan L, Bagchi D, Das DK, Bertelli A, Maulik N (2006) Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1. Cell Biochem Biophys 44:43–49

    PubMed  CAS  Google Scholar 

  21. 21.

    Das S, Cordis GA, Maulik N, Das DK (2005) Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. Am J Physiol Heart Circ Physiol 288:H328–H335

    PubMed  CAS  Google Scholar 

  22. 22.

    Das S, Falchi M, Bertelli A, Maulik N, Das DK (2006) Attenuation of ischemia/reperfusion injury in rats by the anti-inflammatory action of resveratrol. Arzneimittelforschung 56:700–706

    PubMed  CAS  Google Scholar 

  23. 23.

    Das S, Fraga CG, Das DK (2006) Cardioprotective effect of resveratrol via HO-1 expression involves p38 map kinase and PI-3-kinase signaling, but does not involve NFkappaB. Free Radic Res 40:1066–1075

    PubMed  CAS  Google Scholar 

  24. 24.

    Das S, Tosaki A, Bagchi D, Maulik N, Das DK (2006) Potentiation of a survival signal in the ischemic heart by resveratrol through p38 mitogen-activated protein kinase/mitogen- and stress-activated protein kinase 1/cAMP response element-binding protein signaling. J Pharmacol Exp Ther 317:980–988

    PubMed  CAS  Google Scholar 

  25. 25.

    Dekkers DH, Bezstarosti K, Gurusamy N, Luijk K, Verhoeven AJ, Rijkers EJ, Demmers JA, Lamers JM, Maulik N, Das DK (2008) Identification by a differential proteomic approach of the induced stress and redox proteins by resveratrol in the normal and diabetic rat heart. J Cell Mol Med 12:1677–1689

    PubMed  CAS  Google Scholar 

  26. 26.

    Lekli I, Szabo G, Juhasz B, Das S, Das M, Varga E, Szendrei L, Gesztelyi R, Varadi J, Bak I, Das DK, Tosaki A (2008) Protective mechanisms of resveratrol against ischemia-reperfusion-induced damage in hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin. Am J Physiol Heart Circ Physiol 294:H859–H866

    PubMed  CAS  Google Scholar 

  27. 27.

    Yen GC, Duh PD, Lin CW (2003) Effects of resveratrol and 4-hexylresorcinol on hydrogen peroxide-induced oxidative DNA damage in human lymphocytes. Free Radic Res 37:509–514

    PubMed  CAS  Google Scholar 

  28. 28.

    Frankel EN, Waterhouse AL, Kinsella JE (1993) Inhibition of human LDL oxidation by resveratrol. Lancet 341:1103–1104

    PubMed  CAS  Google Scholar 

  29. 29.

    Miller NJ, Rice-Evans CA (1995) Antioxidant activity of resveratrol in red wine. Clin Chem 41:1789

    PubMed  CAS  Google Scholar 

  30. 30.

    Hebbar V, Shen G, Hu R, Kim BR, Chen C, Korytko PJ, Crowell JA, Levine BS, Kong AN (2005) Toxicogenomics of resveratrol in rat liver. Life Sci 76:2299–2314

    PubMed  CAS  Google Scholar 

  31. 31.

    Dore S (2002) Decreased activity of the antioxidant heme oxygenase enzyme: implications in ischemia and in Alzheimer’s disease. Free Radic Biol Med 32:1276–1282

    PubMed  CAS  Google Scholar 

  32. 32.

    Kim YA, Kim GY, Park KY, Choi YH (2007) Resveratrol inhibits nitric oxide and prostaglandin E2 production by lipopolysaccharide-activated C6 microglia. J Med Food 10:218–224

    PubMed  CAS  Google Scholar 

  33. 33.

    Zhuang H, Kim YS, Koehler RC, Dore S (2003) Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann N Y Acad Sci 993:276–286 discussion 287–278

    PubMed  CAS  Google Scholar 

  34. 34.

    Juan SH, Cheng TH, Lin HC, Chu YL, Lee WS (2005) Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells. Biochem Pharmacol 69:41–48

    PubMed  CAS  Google Scholar 

  35. 35.

    Olas B, Wachowicz B, Szewczuk J, Saluk-Juszczak J, Kaca W (2001) The effect of resveratrol on the platelet secretory process induced by endotoxin and thrombin. Microbios 105:7–13

    PubMed  CAS  Google Scholar 

  36. 36.

    Orsini F, Pelizzoni F, Verotta L, Aburjai T, Rogers CB (1997) Isolation, synthesis, and antiplatelet aggregation activity of resveratrol 3-O-beta-D-glucopyranoside and related compounds. J Nat Prod 60:1082–1087

    PubMed  CAS  Google Scholar 

  37. 37.

    Soleas GJ, Diamandis EP, Goldberg DM (1997) Resveratrol: a molecule whose time has come? and gone? Clin Biochem 30:91–113

    PubMed  CAS  Google Scholar 

  38. 38.

    Shen MY, Hsiao G, Liu CL, Fong TH, Lin KH, Chou DS, Sheu JR (2007) Inhibitory mechanisms of resveratrol in platelet activation: pivotal roles of p38 MAPK and NO/cyclic GMP. Br J Haematol 139:475–485

    PubMed  CAS  Google Scholar 

  39. 39.

    Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218–220

    PubMed  CAS  Google Scholar 

  40. 40.

    van Ginkel PR, Sareen D, Subramanian L, Walker Q, Darjatmoko SR, Lindstrom MJ, Kulkarni A, Albert DM, Polans AS (2007) Resveratrol inhibits tumor growth of human neuroblastoma and mediates apoptosis by directly targeting mitochondria. Clin Cancer Res 13:5162–5169

    PubMed  Google Scholar 

  41. 41.

    Trincheri NF, Nicotra G, Follo C, Castino R, Isidoro C (2007) Resveratrol induces cell death in colorectal cancer cells by a novel pathway involving lysosomal cathepsin D. Carcinogenesis 28:922–931

    PubMed  CAS  Google Scholar 

  42. 42.

    Su JL, Yang CY, Zhao M, Kuo ML, Yen ML (2007) Forkhead proteins are critical for bone morphogenetic protein-2 regulation and anti-tumor activity of resveratrol. J Biol Chem 282:19385–19398

    PubMed  CAS  Google Scholar 

  43. 43.

    Harper CE, Patel BB, Wang J, Arabshahi A, Eltoum IA, Lamartiniere CA (2007) Resveratrol suppresses prostate cancer progression in transgenic mice. Carcinogenesis 28:1946–1953

    PubMed  CAS  Google Scholar 

  44. 44.

    Bhardwaj A, Sethi G, Vadhan-Raj S, Bueso-Ramos C, Takada Y, Gaur U, Nair AS, Shishodia S, Aggarwal BB (2007) Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells. Blood 109:2293–2302

    PubMed  CAS  Google Scholar 

  45. 45.

    Abd El-Mohsen M, Bayele H, Kuhnle G, Gibson G, Debnam E, Kaila Srai S, Rice-Evans C, Spencer JP (2006) Distribution of [3H] trans-resveratrol in rat tissues following oral administration. Br J Nutr 96:62–70

    PubMed  CAS  Google Scholar 

  46. 46.

    Sun C, Hu Y, Liu X, Wu T, Wang Y, He W, Wei W (2006) Resveratrol downregulates the constitutional activation of nuclear factor-kappaB in multiple myeloma cells, leading to suppression of proliferation and invasion, arrest of cell cycle, and induction of apoptosis. Cancer Genet Cytogenet 165:9–19

    PubMed  CAS  Google Scholar 

  47. 47.

    Busquets S, Ametller E, Fuster G, Olivan M, Raab V, Argiles JM, Lopez-Soriano FJ (2007) Resveratrol, a natural diphenol, reduces metastatic growth in an experimental cancer model. Cancer Lett 245:144–148

    PubMed  CAS  Google Scholar 

  48. 48.

    Benitez DA, Pozo-Guisado E, Alvarez-Barrientos A, Fernandez-Salguero PM, Castellon EA (2007) Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines. J Androl 28:282–293

    PubMed  CAS  Google Scholar 

  49. 49.

    Hwang JT, Kwak DW, Lin SK, Kim HM, Kim YM, Park OJ (2007) Resveratrol induces apoptosis in chemoresistant cancer cells via modulation of AMPK signaling pathway. Ann N Y Acad Sci 1095:441–448

    PubMed  CAS  Google Scholar 

  50. 50.

    Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR, Kim AL (2007) Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol Appl Pharmacol 224:274–283

    PubMed  CAS  Google Scholar 

  51. 51.

    Cecchinato V, Chiaramonte R, Nizzardo M, Cristofaro B, Basile A, Sherbet GV, Comi P (2007) Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells. Biochem Pharmacol 74:1568–1574

    PubMed  CAS  Google Scholar 

  52. 52.

    Kundu JK, Shin YK, Kim SH, Surh YJ (2006) Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity. Carcinogenesis 27:1465–1474

    PubMed  CAS  Google Scholar 

  53. 53.

    Candelario-Jalil E, de Oliveira AC, Graf S, Bhatia HS, Hull M, Munoz E, Fiebich BL (2007) Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J Neuroinflammation 4:25

    PubMed  Google Scholar 

  54. 54.

    Kim YA, Kim GY, Park KY, Choi YH (2007) Resveratrol inhibits nitric oxide and prostaglandin E2 production by lipopolysaccharide-activated C6 microglia. J Med Food 10:218–224

    PubMed  CAS  Google Scholar 

  55. 55.

    Sharma S, Chopra K, Kulkarni SK, Agrewala JN (2007) Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway. Clin Exp Immunol 147:155–163

    PubMed  CAS  Google Scholar 

  56. 56.

    Singh NP, Hegde VL, Hofseth LJ, Nagarkatti M, Nagarkatti P (2007) Resveratrol (trans-3, 5, 4′-trihydroxystilbene) ameliorates experimental allergic encephalomyelitis, primarily via induction of apoptosis in T cells involving activation of aryl hydrocarbon receptor and estrogen receptor. Mol Pharmacol 72:1508–1521

    PubMed  CAS  Google Scholar 

  57. 57.

    Bertelli A, Falchi M, Dib B, Pini E, Mukherjee S, Das DK (2008) Analgesic resveratrol? Antioxid Redox Signal 10:403–404

    PubMed  CAS  Google Scholar 

  58. 58.

    Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, Neri C (2005) Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet 37:349–350

    PubMed  CAS  Google Scholar 

  59. 59.

    Marambaud P, Zhao H, Davies P (2005) Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem 280:37377–37382

    PubMed  CAS  Google Scholar 

  60. 60.

    Karlsson J, Emgard M, Brundin P, Burkitt MJ (2000) Trans-resveratrol protects embryonic mesencephalic cells from tert-butyl hydroperoxide: electron paramagnetic resonance spin trapping evidence for a radical scavenging mechanism. J Neurochem 75:141–150

    PubMed  CAS  Google Scholar 

  61. 61.

    Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342

    PubMed  CAS  Google Scholar 

  62. 62.

    Miyazaki R, Ichiki T, Hashimoto T, Inanaga K, Imayama I, Sadoshima J, Sunagawa K (2008) SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 28:1263–1269

    PubMed  CAS  Google Scholar 

  63. 63.

    Borra MT, Smith BC, Denu JM (2005) Mechanism of human SIRT1 activation by resveratrol. J Biol Chem 280:17187–17195

    PubMed  CAS  Google Scholar 

  64. 64.

    Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, Bedalov A, Kennedy BK (2005) Substrate-specific activation of sirtuins by resveratrol. J Biol Chem 280:17038–17045

    PubMed  CAS  Google Scholar 

  65. 65.

    Jiang WJ (2008) Sirtuins: novel targets for metabolic disease in drug development. Biochem Biophys Res Commun 373:341–344

    PubMed  CAS  Google Scholar 

  66. 66.

    Guarente L (2007) Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol 72:483–488

    PubMed  CAS  Google Scholar 

  67. 67.

    Howitz KT et al (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191–196

    PubMed  CAS  Google Scholar 

  68. 68.

    Griswold AJ, Chang KT, Runko AP, Knight MA, Min KT (2008) Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila. Proc Natl Acad Sci USA 105:8673–8678

    PubMed  CAS  Google Scholar 

  69. 69.

    Gruber J, Tang SY, Halliwell B (2007) Evidence for a trade-off between survival and fitness caused by resveratrol treatment of Caenorhabditis elegans. Ann N Y Acad Sci 1100:530–542

    PubMed  CAS  Google Scholar 

  70. 70.

    Terzibasi E, Valenzano DR, Cellerino A (2007) The short-lived fish Nothobranchius furzeri as a new model system for aging studies. Exp Gerontol 42:81–89

    PubMed  CAS  Google Scholar 

  71. 71.

    Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, Moncada S, Carruba MO (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314–317

    PubMed  CAS  Google Scholar 

  72. 72.

    Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122

    PubMed  CAS  Google Scholar 

  73. 73.

    Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450:712–716

    PubMed  CAS  Google Scholar 

  74. 74.

    Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, De Oliveira RM, Leid M, McBurney MW, Guarente L (2004) Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-g. Nature 429:771–776

    PubMed  CAS  Google Scholar 

  75. 75.

    Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004) Modulation of NF-kB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23:2369–2380

    PubMed  CAS  Google Scholar 

  76. 76.

    Zhang J (2006) Resveratrol inhibits insulin responses in a SirT1-independent pathway. Biochem J 397:519–527

    PubMed  CAS  Google Scholar 

  77. 77.

    Blüher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 24:572–574

    Google Scholar 

  78. 78.

    Kaestner KH, Knochel W, Martinez DE (2000) Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev 14:142–146

    PubMed  CAS  Google Scholar 

  79. 79.

    Greer EL, Brunet A (2005) FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24:7410–7425

    PubMed  CAS  Google Scholar 

  80. 80.

    Accili D, Arden KC (2004) FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 117:421–426

    PubMed  CAS  Google Scholar 

  81. 81.

    Barthel A, Schmoll D, Unterman TG (2005) FoxO proteins in insulin action and metabolism. Trends Endocrinol Metab 16:183–189

    PubMed  CAS  Google Scholar 

  82. 82.

    Coffer P (2003) OutFOXing the grim reaper: novel mechanisms regulating longevity by forkhead transcription factors. Sci STKE 2003, PE39

  83. 83.

    Morris BJ (2005) A forkhead in the road to longevity: the molecular basis of lifespan becomes clearer. J Hypertens 23:1285–1309

    PubMed  CAS  Google Scholar 

  84. 84.

    Huang H, Tindall DJ (2006) FOXO factors: a matter of life and death. Future Oncol 2:83–89

    PubMed  CAS  Google Scholar 

  85. 85.

    Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857–868

    PubMed  CAS  Google Scholar 

  86. 86.

    Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278:1319–1322

    PubMed  CAS  Google Scholar 

  87. 87.

    Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389:994–999

    PubMed  CAS  Google Scholar 

  88. 88.

    Johnson TE (1990) Increased life-span of age-1 mutants in Caenorhabditis elegans and lower Gompertz rate of aging. Science 249:908–912

    PubMed  CAS  Google Scholar 

  89. 89.

    Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461–464

    PubMed  CAS  Google Scholar 

  90. 90.

    Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382:536–539

    PubMed  CAS  Google Scholar 

  91. 91.

    Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277:942–946

    PubMed  CAS  Google Scholar 

  92. 92.

    Biggs WH, Meisenhelder J, Hunter T, Cavenee WK, Arden KC (1999) Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci USA 96:7421–7426

    PubMed  CAS  Google Scholar 

  93. 93.

    Takaishi H, Konishi H, Matsuzaki H, Ono Y, Shirai Y, Saito N, Kitamura T, Ogawa W, Kasuga M, Kikkawa U, Nishizuka Y (1999) Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. Proc Natl Acad Sci USA 96:11836–11841

    PubMed  CAS  Google Scholar 

  94. 94.

    Brunet A, Kanai F, Stehn J, Xu J, Sarbassova D, Frangioni JV, Dalal SN, DeCaprio JA, Greenberg ME, Yaffe MB (2002) 14–3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport. J Cell Biol 156:817–828

    PubMed  CAS  Google Scholar 

  95. 95.

    Dougherty MK, Morrison DK (2004) Unlocking the code of 14–3-3. J Cell Sci 117:1875–1884

    PubMed  CAS  Google Scholar 

  96. 96.

    Dudley JI, Lekli I, Mukherjee S, Das M, Bertelli AA, Das DK (2008) Does white wine qualify for French paradox? Comparison of the cardioprotective effects of red and white wines and their constituents: resveratrol, tyrosol, and hydroxytyrosol. J Agric Food Chem 56:9362–9373

    PubMed  CAS  Google Scholar 

  97. 97.

    Kirkwood TB, Austad SN (2000) Why do we age? Nature 408:233–238

    PubMed  CAS  Google Scholar 

  98. 98.

    Essers MA, Weijzen S, de Vries-Smits AM, Saarloos I, de Ruiter ND, Bos JL, Burgering BM (2004) FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK. EMBO J 23:4802–4812

    PubMed  CAS  Google Scholar 

  99. 99.

    Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ, Tissenbaum HA (2005) JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc Natl Acad Sci USA 102:4494–4499

    PubMed  CAS  Google Scholar 

  100. 100.

    Wang MC, Bohmann D, Jasper H (2005) JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell 121:115–125

    PubMed  CAS  Google Scholar 

  101. 101.

    Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I (2004) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307(5708):426–430

    PubMed  Google Scholar 

  102. 102.

    Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ (2006) Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 91(1):295–299

    PubMed  CAS  Google Scholar 

  103. 103.

    Luk T, Malam Z, Marshall JC (2008) Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity. J Leukoc Biol 83(4):804–816

    PubMed  CAS  Google Scholar 

  104. 104.

    Silva RM, Duarte IC, Paredes JA, Lima-Costa T, Perrot M, Boucherie H, Goodfellow BJ, Gomes AC, Mateus DD, Moura GR, Santos MA (2009) The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation. PLoS One 4(4):e5212

    PubMed  Google Scholar 

  105. 105.

    Wang T, Zhang X, Bheda P, Revollo JR, Imai S, Wolberger C (2006) Structure of Nampt/PBEF/visfatin, a mammalian NAD + biosynthetic enzyme. Nat Struct Mol Biol 13(7):661–662

    PubMed  CAS  Google Scholar 

  106. 106.

    Marshall JC, Malam Z, Jia S (2007) Modulating neutrophil apoptosis. Novartis Found Symp 280:53–66 discussion 67–72, 160–164

    PubMed  CAS  Google Scholar 

  107. 107.

    Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA (2008) A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One 3(6):e2264

    PubMed  Google Scholar 

  108. 108.

    Moskovitz J, Bar-Noy S, Williams WM, Requena J, Berlett BS, Stadtman ER (2001) Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals. Proc Natl Acad Sci USA 98(23):12920–12925

    PubMed  CAS  Google Scholar 

  109. 109.

    Ruan H, Tang XD, Chen ML, Joiner ML, Sun G, Brot N, Weissbach H, Heinemann SH, Iverson L, Wu CF, Hoshi T (2002) High-quality life extension by the enzyme peptide methionine sulfoxide reductase. Proc Natl Acad Sci USA 99:2748–2753

    PubMed  CAS  Google Scholar 

  110. 110.

    Grubisha O, Smith BC, Denu JM (2005) Small molecule regulation of Sir2 protein deacetylases. FEBS J. 272:4607–4616

    PubMed  CAS  Google Scholar 

  111. 111.

    Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA (2003) Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423(6936):181–185

    PubMed  CAS  Google Scholar 

  112. 112.

    Revollo JR, Grimm AA, Imai S (2004) The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem. 279:50754–50763

    PubMed  CAS  Google Scholar 

  113. 113.

    Streppel MT, Ocke MC, Boshulzen HC, Kok FJ, Kromhout D (2009) Long-term wine consumption is related to cardiovascular mortality and life expectancy independently of moderate alcohol intake: the Zutphen Study. J Epidemiol Community Health 63:534–540

    PubMed  CAS  Google Scholar 

  114. 114.

    Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425(6954):191–196

    PubMed  CAS  Google Scholar 

  115. 115.

    Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 8:157–168

    PubMed  CAS  Google Scholar 

  116. 116.

    Pacholec M, Chrunyk B, Cunningham D, Flynn D, Griffith D, Griffor M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K (2010) SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 285:8340–8351

    Google Scholar 

  117. 117.

    Cumine S, Kim KW, Lu S-C, Atangan L, Wang M (2009) Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Design 74:619–624

    Google Scholar 

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This study was supported by NH HL 34360, HL22559 and HL33889.

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Correspondence to Dipak K. Das.

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An erratum to this article can be found at

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Das, D.K., Mukherjee, S. & Ray, D. Resveratrol and red wine, healthy heart and longevity. Heart Fail Rev 15, 467–477 (2010).

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  • Resveratrol
  • Red wine
  • White wine
  • Cardioprotection
  • Longevity genes
  • Anti-aging
  • SIRT
  • FoxO
  • PBEF