Resveratrol: A Sirtuin Activator and The Fountain of Youth

Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

Abstract


BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life.

CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan.

SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.”

KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator


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Della-Morte D, Ricordi C, Rundek T. The fountain of youth: Role of sirtuins in aging and regenerative medicine. Regen Med. 2013; 8: 681-3, CrossRef.

Willcox BJ, Willcox DC. Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa: controversies and clinical implications. Curr Opin Clin Nutr Metab Care. 2014; 17: 51-8, CrossRef.

Mizushima S, Moriguchi EH, Ishikawa P, Hekman P, Nara Y, Mimura G, et al. Fish intake and cardiovascular risk among middle-aged Japanese in Japan and Brazil. J Cardiovasc Risk. 1997; 4: 191-9, CrossRef.

Fontana L, Partridge L, Longo VD. Extending healthy life span - From yeast to humans. Science. 2010; 328, 321-6, CrossRef.

De Cabo R, Carmona-Gutierrez D, Bernier, Hall MN, Madeo F. The search for antiaging interventions: from elixirs to fasting regimens. Cell. 2014; 157: 1515-26, CrossRef.

Dali-Youcef N, Lagouge M, Froelich S, Koehl C, Schoonjans K, Auwerx J. Sirtuins: the ‘magnificent seven’, function, metabolism and longevity. Ann Med. 2007; 39: 335-45, CrossRef.

Corbi G, Conti V, Scapagnini G, Filippelli A, Ferrara N. Role of sirtuins, calorie restriction and physical activity in aging. Front Biosci (Elite Ed). 2012; 4, 768-78, CrossRef.

Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003; 425: 191-6, CrossRef.

Haigis MC, Guarente LP. Mammalian sirtuins - Emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006; 20: 2913-21, CrossRef.

Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaras K, et al. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis. 2010; 1: e10, CrossRef.

Rando TA. Stem cells, ageing and the quest for immortality. Nature. 2006; 441: 1080-6, CrossRef.

Rossi DJ, Jamieson CH, Weissman IL. Stems cells and the pathways to aging and cancer. Cell. 2008; 132: 681-96, CrossRef.

Sahin E, Depinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature. 2010; 464: 520-8, CrossRef.

Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, et al. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature. 2006; 443: 421-6, CrossRef.

Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005; 120: 483-95, CrossRef.

Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006; 12: 446-51, CrossRef.

Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature. 2004; 431: 997-1002, CrossRef.

Miyamoto K, Araki KY, Naka K, Arai F, Takubo K, Yamazaki S, et al. Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell. 2007; 1: 101-12, CrossRef.

Paik JH, Ding Z, Narurkar R, Ramkissoon S, Muller F, Kamoun WS, et al. FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell. 2009; 5: 540–53, CrossRef.

Renault VM, Rafalski VA, Morgan AA, Salih DA, Brett JO, Webb AE, et al. FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell. 2009; 5: 527-39, CrossRef.

Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell. 2007; 128: 325-39, CrossRef.

Brown K, Xie S, Qiu X, Mohrin M, Shin J, Liu Y, et al. SIRT3 reverses aging-associated degeneration. Cell Rep. 2013; 3: 319-27, CrossRef.

Mercken EM, Carboneau BA, Krzysik-Walker SM, de Cabo R. Of mice and men: the benefits of caloric restriction, exercise, and mimetics. Ageing Res Rev. 2012; 11: 390-8, CrossRef.

Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr. 2005; 82 (Suppl 1): S222-5, PMID.

Gurwitz JH, Goldberg RJ, Gore JM. Coronary thrombolysis for the elderly? JAMA. 1991; 265: 1720-3, CrossRef.

Ungvari Z, Kaley G, de Cabo R, Sonntag WE, Csiszar A. Mechanisms of vascular aging: new perspectives. J Gerontol A Biol Sci Med Sci. 2010; 65: 1028-41, CrossRef.

Ungvari Z, Bailey-Downs L, Gautam T, Sosnowska D, Wang M, Monticone RE, et al. Age-associated vascular oxidative stress, Nrf2 dysfunction, and NF-{kappa}B activation in the nonhuman primate Macaca mulatta. J Gerontol A Biol Sci Med. 2011; 66: 866-75, CrossRef.

Lakatta EG, Wang M, Najjar S. Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels. Med Clin North Am. 2009; 93: 583-604, CrossRef.

Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Heart disease and stroke statistics - 2010 update: A report from the American Heart Association. Circulation. 2010; 12: e46-e215, CrossRef.

Lakatta EG. The reality of aging viewed from the arterial wall. Artery Res. 2013; 7: 73-80, CrossRef.

Wang M, Monticone RE, Lakatta EG. Arterial aging: a journey into subclinical arterial disease. Curr Opin Nephrol Hypertens. 2010; 19: 201-7, CrossRef.

Wang M, Lakatta EG. Central arterial aging: humans to molecules. In: Safar M, O'Rourke MF, editor. Handbook of Hypertension: Arterial Stiffness in Hypertension. New York: Elsevier; 2006. p.137-160, NLMID.

Wang M, Khazan B, Lakatta EG. Central arterial aging and angiotensin II signaling. Curr Hypertens Rev. 2010; 6: 266-81, CrossRef.

Wang M, Jiang L, Monticone RE, Lakatta EG. Proinflammation: the key to arterial aging. Trends Endocrinol Metab. 2014; 25: 72-9, CrossRef.

World Health Organization. Joint WHO/FAO expert consultation on: Diet, nutrition and the prevention of the chronic diseases. Geneva: World Health Organization; 2003, article.

World Health Organization. Preventing chronic diseases: a vital investment: WHO global report. Geneva: WHO Press; 2005, article.

Department of Health and Human Services, National Center for Chronic Disease Prevention and Health Promotion. Chronic disease, the public health challenge of the 21st century. Atlanta: Centers for Disease Control and Prevention; 2009, article.

Willcox BJ, Willcox DC, Todoriki H, Fujiyoshi A, Yano K, He Q, et al. Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world’s longest-lived people and its potential impact on morbidity and life span. Ann NY Acad Sci. 2007; 1114: 434-55, CrossRef.

Willcox DC, Willcox BJ, Todoriki H, Suzuki M. The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load. J Am Coll Nutr. 2009; 28 (Suppl 4): S500-16, CrossRef.

Willcox DC, Willcox BJ, Yasura S, Ashitomi I, Suzuki M. Gender gap in healthspan and life expectancy in Okinawa: health behaviours. Asian J Gerontol Geriatr. 2012; 7: 49-58, article.

Gavrilova NS, Gavrilov LA. Comments on dietary restriction, Okinawa diet and longevity. Gerontology. 2012; 58: 221-3, CrossRef.

Willcox DC, Willcox BJ, Todoriki H, Curb JD, Suzuki M. Caloric restriction and human longevity: what can we learn from the Okinawans? Biogerontology. 2006; 7: 173-7, CrossRef.

Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009; 325: 201-4, CrossRef.

Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012; 489: 318-21, CrossRef.

Weindruch R, Walford RL, Fligiel S, Guthrie D. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J Nutr. 1986; 116: 641-54, PMID.

Koubova J, Guarente L. How does calorie restriction work? Genes Dev. 2003; 17: 313-21, CrossRef.

Anderson RM, Weindruch R. The caloric restriction paradigm: implications for healthy human aging. Am J Hum Biol. 2012; 24: 101-6, CrossRef.

Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996; 273: 59-63, CrossRef.

Mercken EM, Crosby SD, Lamming DW, JeBailey L, Krzysik-Walker S, Villareal DT, et al. Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell. 2013; 12: 645-51, CrossRef.

Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005; 39: 359-407, CrossRef.

Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, et al. Calorie Restriction and SIRT3 Trigger Global Reprogramming of the Mitochondrial Protein Acetylome. Mol Cell. 2013; 49: 186-99, CrossRef.

Longo VD, Mattson MP. Fasting: molecular mechanism and clinical application. Cell Metab. 2014; 19: 181-92, CrossRef.

Davinelli S, Willcox DC, Scapagnini G. Extending healthy ageing: nutrient sensitive pathway and centenarian population. Immun Ageing. 2012; 9: 9, CrossRef.

Murakami A, Ishida H, Kubo K, Furukawa I, Ikeda Y, Yonaha M, et al. Suppressive effects of Okinawan food items on free radical generation from stimulated leukocytes and identification of some active constituents: implications for the prevention of inflammation-associated carcinogenesis. Asian Pacific J Cancer Prev. 2005; 6: 437-48, PMID.

Huffman DM. Exercise as a calorie restriction mimetic: implications for improving healthy aging and longevity. Interdiscip Top Gerontol. 2010; 37: 157-74, CrossRef.

Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence. CMAJ. 2006; 174: 801-9, CrossRef.

Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk. Rejuvenation Res. 2007; 10: 225-34, CrossRef.

Lee IM, Skerrett PJ. Physical activity and all-cause mortality: what is the dose-response relation? Med Sci Sports Exerc. 2001; 33 (Suppl 6): S459-71, CrossRef.

Huffman DM, Moellering DR, Grizzle WE, Stockard CR, Johnson MS, Nagy TR. Effect of exercise and calorie restriction on biomarkers of aging in mice. Am J Physiol Regul Integr Comp Physiol. 2008; 294: R1618-27, CrossRef.

Nicklas BJ, Wang X, You T, Lyles MF, Demons J, Easter L, et al. Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: a randomized, controlled trial. Am J Clin Nutr. 2009; 89: 1043-52, CrossRef.

Haigis MC, Sinclair DA. Mammalian sirtuins: Biological insights and disease relevance. Annu Rev Pathol. 2010; 5: 253-95, CrossRef.

Feldman JL, Dittenhafer-Reed KE, Denu JM. Sirtuin catalysis and regulation. J Biol Chem. 2012; 287: 42419-27, CrossRef.

Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 2001; 107: 149-59, CrossRef.

Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004; 303: 2011-5, CrossRef.

Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005; 434: 113-8, CrossRef.

Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004; 23: 2369-80, CrossRef.

Silva JP, Wahlestedt C. Role of Sirtuin 1 in metabolic regulation. Drug Discov Today. 2010; 15: 781-91, CrossRef.

Cantó C, Jiang LQ, Deshmukh AS, Mataki C, Coste A, Lagouge M, et al. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab. 2010; 11: 213-9, CrossRef.

Hallows WC, Yu W, Denu JM. Regulation of glycolytic enzyme phosphoglycerate mutase-1 by Sirt1 protein-mediated deacetylation. J Biol Chem. 2012; 287: 3850-8, CrossRef.

Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, et al. Adiponectin and adipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature. 2010; 464: 1313-9, CrossRef.

Purushotham A, Xu Q, Li X. Systemic SIRT1 insufficiency results in disruption of energy homeostasis and steroid hormone metabolism upon high-fat-diet feeding. FASEB J. 2012; 26: 656-67, CrossRef.

Wang RH, Kim HS, Xiao C, Xu X, Gavrilova O, Deng CX. Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance. J Clin Invest. 2011; 121: 4477-90, CrossRef.

Villalba JM, de Cabo R, Alcain FJ. A patent review of sirtuin activators: an update. Expert Opin Ther Patents. 2012; 22: 355-67, CrossRef.

Kenyon CJ. The genetics of ageing. Nature. 2010; 464: 504-12, CrossRef.

Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011; 12: 21-35, CrossRef.

Demontis F, Perrimon N. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell. 2010; 143: 813-25, CrossRef.

Durieux J, Wolff S, Dillin A. The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell. 2011; 144: 79-91, CrossRef.

Guarente L. Mitochondria - A nexus for aging, calorie restriction, and sirtuins? Cell. 2008; 132: 171-6, CrossRef.

Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010; 5: 253-95, CrossRef.

Houtkooper RH, Canto ́ C, Wanders RJ, Auwerx J. The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr Rev. 2010; 31: 194-223, CrossRef.

Chalkiadaki A, Guarente L. Sirtuins mediate mammalian metabolic responses to nutrient availability. Nat Rev Endocrinol. 2012; 8: 287-96, CrossRef.

Houtkooper RH, Auwerx J. Exploring the therapeutic space around NAD+. J. Cell Biol. 2012; 199: 205-9, CrossRef.

Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011; 14: 528-36, CrossRef.

Canto ́ C, Auwerx J. Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)? Pharmacol Rev. 2012; 64: 166-87, CrossRef.

Mouchiroud L, Houtkooper RH, Moullen N, Katsyuba E, Ryu D, Canto C, et al. The NAD+/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell. 2013; 154: 430-41, CrossRef.

Houtkooper RH, Williams RW, Auwerx J. Metabolic networks of longevity. Cell. 2010; 142: 9-14, CrossRef.

Lin SJ, Defossez PA, Guarente L. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science. 2000; 289: 2126-8, CrossRef.

Rogina B, Helfand SL. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA. 2004; 101: 15998-6003, CrossRef.

Wang Y, Tissenbaum HA. Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev. 2006; 127: 48-56, CrossRef.

Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, Culotta VC, et al. 2002. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature. 2002; 418: 344-8, CrossRef.

Lin SJ, Ford E, Haigis M, Liszt G, Guarente L. Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev. 20014; 18: 12-6, CrossRef.

Kaeberlein M, Kirkland KT, Fields S, Kennedy BK. Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol. 2004; 2: E296, CrossRef.

Kaeberlein M, Hu D, Kerr EO, Tsuchiya M, Westman EA, Dang N, et al. Increased life span due to calorie restriction in respiratory-deficient yeast. PLoS Genet. 2005; 1: e69, CrossRef.

Takaoka MJ. Of the phenolic substances of white hellebore (Veratrum grandiflorum Loes. fil.). J Faculty Sci Hokkaido Imperial University. 1940; 3: 1-16.

Nonomura S, Kanagawa H, Makimoto A. [Chemical Constituents of Polygonaceous Plants. I. Studies on the Components of KO-JO-KON. (Polygonum Cuspidatum Sieb. Et Zucc.)]. Yakugaku Zasshi. 1963; 83: 988-90, PMID.

Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine. Am J Enol Vitic. 1992; 43: 49-52, article.

Liu BL, Zhang X, Zhang W, Zhen HN. New enlightenment of French Paradox: resveratrol's potential for cancer chemoprevention and anti-cancer therapy. Cancer Biol Ther. 2007; 6: 1833-6, CrossRef.

Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997; 275: 218-20, CrossRef.

Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006; 5: 493-506, CrossRef.

Vang O, Ahmad N, Baile CA, Baur JA, Brown K, Csiszar A, D, et al. What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS One. 2011; 6: e19881, CrossRef.

Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006; 444: 337-42, CrossRef.

Lagouge M, Argmann C, Gerhart‐Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC‐1alpha. Cell. 2006; 127: 1109-22, CrossRef.

Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004; 430: 686-9, CrossRef.

Agarwal B, Baur JA. Resveratrol and life extension. Ann NY Acad Sci. 2011; 1215: 138-43, CrossRef.

Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L. Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech Ageing Dev. 2007; 128: 546-52, CrossRef.

Valenzano DR, 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, CrossRef.

Timmers S, Auwerx J, Schrauwen P. The journey of resveratrol from yeast to human. Aging (Albany NY). 2012; 4: 146-58, PMID.

Halliwell B. Dietary polyphenols: Good, bad, or indifferent for your health? Cardiovasc Res. 2007; 73: 341-7, CrossRef.

Mukherjee S, Dudley JI, Das DK. Dose-dependency of resveratrol in providing health benefits. Dose Response. 2010; 8: 478-500, CrossRef.

Subbaramaiah K, Chung WJ, Michaluart P, Telang N, Tanabe T, Inoue H, et al. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J Biol Chem. 1998; 273: 21875-82, CrossRef.

Stewart JR, Ward NE, Ioannides CG, O'Brian CA. Resveratrol preferentially inhibits protein kinase C-catalyzed phosphorylation of a cofactor-independent, arginine-rich protein substrate by a novel mechanism. Biochemistry. 1999; 38: 13244-51, CrossRef.

Schneider Y, Vincent F, Duranton B, Badolo L, Gossé F, Bergmann C, et al. Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Lett. 2000; 158: 85-91, CrossRef.

Khanduja KL, Bhardwaj A, Kaushik G. Resveratrol inhibits N-nitrosodiethylamine-induced ornithine decarboxylase and cyclooxygenase in mice. J Nutr Sci Vitaminol (Tokyo). 2004; 50: 61-5, CrossRef.

Fu ZD, Cao Y, Wang KF, Xu SF, Han R. [Chemopreventive effect of resveratrol to cancer]. Ai Zheng. 2004; 23: 869-73, PMID.

Afaq F, Adhami VM, Ahmad N. Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice. Toxicol Appl Pharmacol. 2003; 186: 28-37, CrossRef.

Kimura Y, Okuda H. Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice. J Nutr. 2001; 131: 1844-9, PMID.

Tseng SH, Lin SM, Chen JC, Su YH, Huang HY, Chen CK, et al. Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats. Clin Cancer Res. 2004; 10: 2190-202, CrossRef.

Yu C, Shin YG, Kosmeder JW, Pezzuto JM, van Breemen RB. Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun Mass Spectrom. 2003; 17: 307-13, CrossRef.

Piver B, Berthou F, Dreano Y, Lucas D. Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett. 2001; 125: 83-91, CrossRef.

Chang TK, Lee WB, Ko HH. Trans-resveratrol modulates the catalytic activity and mRNA expression of the procarcinogen-activating human cytochrome P450 1B1. Can J Physiol Pharmacol. 2000; 78: 874-81, CrossRef.

Chan WK, Delucchi AB. Resveratrol, a red wine constituent, is a mechanism-based inactivator of cytochrome P450 3A4. Life Sci. 2000; 67: 3103-12, CrossRef.

Ciolino HP, Daschner PJ, Yeh GC. Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor. Cancer Res. 1998; 58: 5707-12, PMID.

Casper RF, Quesne M, Rogers IM, Shirota T, Jolivet A, Milgrom E, et al. Resveratrol has antagonist activity on the aryl hydrocarbon receptor: implications for prevention of dioxin toxicity. Mol Pharmacol. 1999; 56: 784-90, PMID.

Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 2004; 24: 2783-840, PMID.

Yu L, Sun ZJ, Wu SL, Pan CE. Effect of resveratrol on cell cycle proteins in murine transplantable liver cancer. World J Gastroenterol. 2003; 9: 2341-3, PMID.

Schneider Y, Duranton B, Gossé F, Schleiffer R, Seiler N, Raul F. Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis. Nutr Cancer. 2001; 39: 102-7, CrossRef.

Reagan-Shaw S, Afaq F, Aziz MH, Ahmad N. Modulations of critical cell cycle regulatory events during chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mouse skin. Oncogene. 2004; 23: 5151-60, CrossRef.

Garvin S, Ollinger K, Dabrosin C. Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Lett. 2006; 231: 113-22, CrossRef.

Provinciali M, Re F, Donnini A, Orlando F, Bartozzi B, Di Stasio G, et al. Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer. 2005; 115: 36-45, CrossRef.

Zhou HB, Chen JJ, Wang WX, Cai JT, Du Q. Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice. World J Gastroenterol. 2005; 11: 280-4, CrossRef.

Kensler T, Guyton K, Egner P, McCarthy T, Lesko S, Akman S. Role of reactive intermediates in tumor promotion and progression. Prog Clin Biol Res. 1995; 391: 103-16, PMID.

Gromadzinska J, Wasowicz W. The role of reactive oxygen species in the development of malignancies. Int J Occup Med Environ Health. 2000; 13: 233-45, PMID.

Kundu JK, Shin YK, Kim SH, Surh YJ. Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity. Carcinogenesis. 2006; 27: 1465-74, CrossRef.

Candelario-Jalil E, de Oliveira A C, Gräf S, Bhatia HS, Hüll M, Muñoz E, et al. Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J Neuroinflammation. 2007; 4: 25, CrossRef.

Kim YA, Kim GY, Park KY, Choi YH. Resveratrol inhibits nitric oxide and prostaglandin E2 production by lipopolysaccharide-activated C6 microglia. J Med Food. 2007; 10: 218-24, CrossRef.

Sharma S, Chopra K, Kulkarni SK, Agrewala JN. Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway. Clin Exp Immunol. 2007; 147: 155-63, CrossRef.

Singh NP, Hegde VL, Hofseth LJ, Nagarkatti M, Nagarkatti P. Resveratrol (trans-3,5,4’-tri-hydroxystilbene) ameliorates experimental allergic encephalomyelitis, primarily via induction of apoptosis in T cells involving activation of aryl hydrocarbon receptor and estrogen receptor. Mol Pharmacol. 2007; 72: 1508-21, CrossRef.

Bertelli A, Falchi M, Dib B, Pini E, Mukherjee S, Das DK. Analgesic resveratrol? Antioxid Redox Signal. 2008; 10: 403-4, CrossRef.

Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, et al. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet. 2005; 37: 349-50, CrossRef.

Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem. 2005; 280: 37377-82, CrossRef.

Karlsson J, Emgard M, Brundin P, Burkitt MJ. trans-resveratrol protects embryonic mesencephalic cells from tert-butyl hydroperoxide: electron paramagnetic resonance spin trapping evidence for a radical scavenging mechanism. J Neurochem. 2000; 75: 141-50, CrossRef.

Da-Pan A, Blanc S, Aujard F. Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC Physiol. 2010; 10: 11, CrossRef.

Da-Pan A, Terrien J, Pifferi F, Botalla R, Hardy I, Marchal J, et al. Caloric restriction or resveratrol supplementation and ageing in a non-human primate: first-year outcome of the RESTRIKAL study in Microcebus murinus. Age (Dordr). 2011; 33: 15-31, CrossRef.

Thompson MM, Jones L, Nasim A, Sayers RD, Bell PR. Angiogenesis in abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 1996; 11: 464-9, CrossRef.

Norata GD, Marchesi P, Passamonti S, Pirillo A, Violi F, Catapano AL. Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice. Atherosclerosis. 2007; 191: 265-71, CrossRef.

Kaneko H, Anzai T, Morisawa M, Kohno T, Nagai T, Anzai A, et al. Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization. Atherosclerosis. 2011; 217: 350-7, CrossRef.

Patel KR, Scott E, Brown VA, Gescher AJ, Stewad WP, Brown K. Clinical Trials of resveratrol. Ann NY Acad Sci. 2011; 1215: 161-9, CrossRef.

Rutanen J, Yaluri N, Modi S, Pihlajamäki J, Vänttinen M, Itkonen P, et al. SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity. Diabetes. 2010; 59: 829-35, CrossRef.

Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des. 2009; 74: 619-24, CrossRef.

Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999; 13: 2570-80, CrossRef.

Baur JA. Resveratrol, sirtuins, and the promise of a DR mimetic. Mech Ageing Dev. 2010; 131: 261-9, CrossRef.

Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008; 8: 157-68, CrossRef.

Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One. 2008; 3: e2264, CrossRef.

Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005; 280: 17187-95, CrossRef.

Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, et al. Substrate-specific activation of sirtuins by resveratrol. J Biol Chem. 2005; 280: 17038-45, CrossRef.

Dasgupta B, Milbrandt J. Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci USA. 2007; 104: 7217-22, CrossRef.

Feige JN, Lagouge M, Canto C, Strehle A, Houten SM, Milne JC, et al. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab. 2008; 8: 347-58, CrossRef.

Park CE, Kim MJ, Lee JH, Min BI, Bae H, Choe W, et al. Resveratrol stimulates glucose transport in C2C12 myotubes by activating AMP‐activated protein kinase. Exp Mol Med. 2007; 39: 222-9, CrossRef.

Zini R, Morin C, Bertelli A, Bertelli AA, Tillement JP. Effects of resveratrol on the rat brain respiratory chain. Drugs Exp Clin Res. 1999; 25: 87-97, PMID.

Hawley SA, Ross FA, Chevtzoff C, Green KA, Evans A, Fogarty S, et al. Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab. 2010; 11: 554-65, CrossRef.

Suchankova G, Nelson LE, Gerhart-Hines Z, Kelly M, Gauthier MS, Saha AK, et al. Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells. Biochem Biophys Res Commun. 2009; 378: 836-41, CrossRef.

Um JH, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, et al. AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes. 2010; 59: 554-63, CrossRef.

Canto C, Auwerx J. AMP-activated protein kinase and its downstream transcriptional pathways. Cell Mol Life Sci. 2010; 67: 3407-23, CrossRef.

Canto C, Auwerx J. Caloric restriction, SIRT1 and longevity. Trends Endocrinol Metab. 2009; 20: 325-31, CrossRef.

Yuen DA, Zhang Y, Thai K, Spring C, Chan L, Guo X, et al. Angiogenic dysfunction in bone marrow-derived early outgrowth cells from diabetic animals is attenuated by SIRT1 activation. Stem Cells Transl Med. 2012; 1: 921-6, CrossRef.

Liu B, Ghosh S, Yang X, Zheng H, Liu X, Wang Z, et al. Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metab. 2012; 16: 738-50, CrossRef.

Bemis JE, Vu CB, Xie R, Nunes JJ, Ng PY, Disch JS, et al. Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators. Bioorg Med Chem Lett. 2009; 19: 2350-3, CrossRef.

Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007; 450: 712-6, CrossRef.

Vu CB, Bemis JE, Disch JS, Ng PY, Nunes JJ, Milne JC, et al. Discovery of imidazo[1,2-b]thiazole derivatives as novel SIRT1 activators. J Med Chem. 2009; 52: 1275-83, CrossRef.

Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, et al. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem. 2006; 281: 21745-54, CrossRef.

Yang T, Chan NY, Sauve AA. Syntheses of nicotinamide riboside and derivatives: effective agents for increasing nicotinamide adenine dinucleotide concentrations in mammalian cells. J Med Chem. 2007; 50: 6458-61, CrossRef.




DOI: https://doi.org/10.18585/inabj.v7i1.16

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