Anti-aging Effect of Resveratrol2010-02-12
Currently, the best way to longevity and good health is through Calorie Restriction. A Chinese Quote: “Eating 80% full leads to longevity”. It allows room for the digestive organs, hence, help to improve digestion and health. However, this concept is not straightforward, according to the recent research studies.
The concept of Calorie Restriction to extend longevity was initially proposed by Mary Crowell and Clive McCay from Cornell University in 1934. Their researches have shown that rats fed on a low calorie diets live nearly twice longer than rats fed on normal diet. Subsequently; in the next fifty years, many researchers have confirmed the similar results of lifespan extension in other animal models.
In 2002, Dr. Luigi Fontana from University of Washington led a calorie restriction studies on 30 volunteers. The study found the older the person, the greater the slowdown of aging and the average age group- 55 years old had an almost similar blood pressure of a 20 year old adult. In 2006, a group of researchers from Salt Lake City discovered the slowed aging effect was actually regulated by a functional gene found in the animal model. All these facts suggested that “Humans can also have a longer lifespan if they keep a calorie restricted diet like in the animal studies”.
The compound regulated by SIRT1 gene is responsible for controlling the expression of a group of enzyme protein (Zymoprotein). In general, higher gene expression level will generate greater biological metabolism and enhance the rate of aging.
In 2003, Dr. Sinclair from Harvard University discovered that SIRT1 enzyme can be activated by resveratrol in yeast; by adding resveratrol in the yeast culture, the lifespan of yeast was doubled.
★ Howitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003; 425: 191-196. （http://www.nature.com/nature/journal/v425/n6954/abs/nature01960.html）
Subsequently, Dr Sinclair continued the studies in mouse models; their report implies that very large doses of resveratrol could offset the unhealthy high-calorie diet. The research group fed the mice a high fat diet and a large daily dose of resveratrol when the mice were 1 year old, middle-aged in mouse terms. The results showed resveratrol can avert the high levels of glucose and insulin in the bloodstream and extended the mice’s lifespan. (Nature. 2006; 444: 337-342., see page 40) Resveratrol may not be able to explain the longevity effect in human, yet it definitely shows significant improvement on the type 2 diabetes.【Note: Dr. Sinclair is a co-founder of Sirtris Pharmaceuticals. In 2008, Sirtris Pharmaceuticals Inc. has been sold for $720 million to International pharmaceutical company. 】
★ Ingram DK, et al. Development of calorie restriction mimetics as a prolongevity strategy. Ann NY Acad Sci. 2004; 1019: 412-423. （http://www3.interscience.wiley.com/journal/118765941/abstract）
★ Sinclair DA. Toward a unified theory of caloric restriction and longevity regulation. Mech Ageing Dev. 2005; 126: 987-1002.
★ Guarente L, Picard F. Calorie restriction—the SIR2 connection. Cell 2005; 120: 473-482.（http://www.cell.com/retrieve/pii/S0092867405001030）
★ Porcu M, Chiarugi A. The emerging therapeutic potential of sirtuin-interacting drugs: from cell death to lifespan extension. Trends Pharmacol Sci. 2005; 26: 94-103.
★ Borra MT, et al. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005; 280: 17187-17195.（http://www.jbc.org/cgi/reprint/280/17/17187）
★ Kaeberlein M, et al. Substrate-specific activation of sirtuins by resveratrol. J Biol Chem. 2005; 280: 17038-17045. （http://www.jbc.org/cgi/reprint/280/17/17038）
★ Valenzano DR, et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol. 2006; 16: 296-300. （http://www.cell.com/current-biology/retrieve/pii/S0960982206010207）
★ Heilbronn LK, et al. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA. 2006; 295: 1539-1548.（http://jama.ama-assn.org/cgi/reprint/295/13/1539）
★ Baur JA, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006; 444: 337-342. (http://www.nature.com/nature/journal/v444/n7117/abs/nature05354.html)
★ Lagouge M, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006; 127: 1109-1122.（http://www.cell.com/retrieve/pii/S0092867406014280）
Beside harmless, Resveratrol is also beneficial for the growth of sperm cells. In other words, Resveratrol can enhance male fertility.
★ Juan ME, et al. Trans-resveratrol, a natural antioxidant from grapes, increases sperm output in healthy rats. J. Nutr. 2005; 135(4): 757 - 760. (http://jn.nutrition.org/cgi/content/abstract/135/4/757)
★ Jiang YG, et al. Resveratrol reestablishes spermatogenesis after testicular injury in rats caused by 2, 5-hexanedione. Chin Med J 2008; 121(13): 1204-1209. (http://www.cmj.org/Periodical/PDF/20087439201740.pdf)
★ Forgács Zs, et al. Effect of resveratrol on the testosterone production of mouse primary leydig cell culture. (http://www.slpk.sk/eldo/2005/002_05/forgacs.pdf)
Resveratrol prevents Alzheimer’s disease.
★ Ignatowicz E, Baer-Dubowska W. Resveratrol, a natural chemopreventive agent against degenerative diseases. Pol J Pharmacol. 2001; 53: 557-569. （http://www.chiroonline.net/_fileCabinet/resveratrol.pdf）
★ Savaskan E, et al. Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity. Gerontology. 2003; 49: 380-383. （http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=73766&Ausgabe=229640&ProduktNr=224091）
★ Marambaud P, et al. Resveratrol promotes clearance of Alzheimer"s disease amyloid-beta peptides. J Biol Chem. 2005; 280: 37377-37382. （http://www.jbc.org/cgi/reprint/280/45/37377）
★ Anekonda TS. Resveratrol—a boon for treating Alzheimer’s disease? Brain Res Rev. 2006; 52: 316-326.
Resveratrol promotes skin rejuvenation.
★ Baxter, RA. Anti-aging properties of resveratrol: review and report of a potent new antioxidant skin care formulation. J Cosmetic Dermatolog 2008; 7:2-7.
Dr Sinclair’s contributions have set off a wave of new research in Resveratrol studies. Below shows some of the latest publications related to Resveratrol in enhancing longevity.