Resveratrol/Red Wine Structure - Wall Street Journal Article

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Resveratrol / Red Wine Structure - Wall Street Journal Article

Research has revealed that resveratrol has anti-aging effects in some animals, extending the lifespan of yeast by 60%, worms and flies by 30%, and fish by about 60%.

Since the 1930s its been known that calorie restriction by about a third can slow the biological forces of aging.  Scientists began to claim that it's possible to mimic the anti-aging effect with a molecule from red wine called resveratrol, reports David Stipp in The Wall Street Journal (10/30/06).  See below link.

Red wine contains resveratrol, but the quantity varies depending on where the grapes are grown, the time of harvest and other factors. In fact, usually only one to three mg of resveratrol per liter of red wine is currently found, even in the most robust red wines. After years of relentless research, a standardized resveratrol extract is now available as a dietary supplement.

Research funded by the Life Extension Foundation showed that a combination of low-dose (20 mg) resveratrol plus grapeseed extract mimicked many of the favorable gene expression changes seen in calorie-restricted animals.

The Wall Street Journal
October 30, 2006; Page A1

Youthful Pursuit
Researchers Seek Key to Antiaging In Calorie Cutback

A Controversial Hypothesis Draws Scientists, Investors;  Will It Work in Humans?  Fighting Fat in Lab Mice

 Resveratrol in Red Wine

MSNBC -- 12-06-2010

Chemicals in Apple Skins, Wine Could Help Fight Alzheimer's by Emily Sohn

A compound found in red wine may extend the human life span and help with Alzheimer's Disease.  A report from the front lines --

Health News
by Vitamins Research Staff

Very low calorie diets are all the rage these days -- but not for the reasons you might think.  Aside from keeping you slender, research shows that if you eat 10 to 30 percent less than the average person, you can also tack years onto your life -- that is, if you can keep up with this type of diet.  For most, constant hunger pangs make drastic calorie cutbacks far too tough to maintain over the long haul.

But what if you could get all of the health benefits of caloric restriction without the grueling dietary demands?  It may sound impossible, but recent research on a unique natural compound suggests that you can have your cake and, eat it too.

Resveratrol, a phytonutrient commonly found in red grapes and wine, has attracted widespread attention for its astounding ability to put the brakes on aging.  Its effects on longevity in mammals was first investigated back in 2006, when scientists discovered that resveratrol supplementation can inhibit complications of obesity -- including enlarged liver, muscle inflammation, and early signs of heart disease and diabetes in overfed mice.1

Soon after, another study added more steam to the theory ... this time showing that large amounts of resveratrol could double physical endurance (including oxygen consumption efficiency and grip strength) in healthy young mice.  As a result, excess calories were more readily burned off and weight gain prevented.2

Scientists still arent sure how to account for these incredible benefits but they think its because resveratrol is able to mimic the effects of caloric restriction (CR) by switching on the "longevity gene" called SIRT1.  Mice with higher levels of SIRT1 (due to genetic alterations or resveratrol consumption) show greater energy expenditure, reduced weight gain, and increased insulin sensitivity -- all in spite of a high-fat, high-calorie diet.3-4  And those arent the only benefits that resveratrol and caloric restriction have in common.

In a study performed in 2007, researchers found that while mice with high-calorie diets lived longer while taking resveratrol, mice in the standard diet group also benefited from resveratrol supplementation showing improved heart function, bone density, motor function, and delayed the onset of cataracts.5  Its effects on heart health are particularly pronounced.  More recent studies reveal that resveratrol mimics the effects of caloric restriction and can inhibit cardiac aging by 90 percent.6

While starvation-free longevity might seem too good to be true, rest assured that its not.

References for "Health News" article:
1. Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-342.

2. Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 Dec 15;127(6):1109-1122.

3. Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschp MH. Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci USA. 2008;105(28):9793-9798.

4. Sun C, Zhang F, Ge X, et al. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab 2007;6:307-319.

5. Pearson KJ, Baur JA, Lewis KN, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008 Aug;8(2):157-168.

6. Barger JL, Kayo T, Vann JM, et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE. 2008 Jun 4;3(6):e2264.

In the August, 2009 issue of The Journal of the Federation of American Societies for Experimental Biology (FASEB Journal), researchers from the University of Singapore and the University of Glasgow in Scotland report their discovery of the mechanism supporting the ability of resveratrol, an antioxidant compound that occurs in red wine, to control acute inflammation.

"Strong acute inflammatory diseases such as sepsis are very difficult to treat and many die every day due to lack of treatment," stated study coauthor Alirio Melendez, who is a senior lecturer on the faculty of medicine at Glasgow Biomedical Research Centre. "Moreover, many survivors of sepsis develop a very low quality of life due to the damage that inflammation causes to several internal organs. The ultimate goal of our study was to identify a potential novel therapy to help in the treatment of strong acute inflammatory diseases."

The scientists tested the effect of pretreatment with several concentrations of resveratrol in cultured white blood cells known as neutrophils derived from mice and humans to which a proinflammatory agent was administered. "Pretreatment of human and mouse neutrophils with resveratrol significantly blocked oxidative burst, leukocyte [white blood cell] migration, degranulation, and inflammatory cytokine production," the authors report. "The anti-inflammatory action of resveratrol was a function of inhibition of sphingosine kinase activity within 5 minutes of exposure, its membrane location, and sphingosine kinase1-mediated calcium ion release. We also provide evidence that the sphingosine kinase inhibitory effect of resveratrol was mediated via its ability to block phospholipase D activity."

In another experiment using mice in which peritonitis was induced with the same proinflammatory agent, pretreatment by injection with resveratrol prevented the strong inflammatory response that was observed in the non-pretreated group. Increases in vascular permeability and neutrophil migration and recruitment were blocked, and levels of proinflammatory cytokines including interleukin-6, interleukin-1B, and tumor necrosis factor-alpha were significantly reduced.

The authors suggest an upstream role for sphingosine kinase in the nuclear factor kappa-beta pathway of inflammation. "In light of its pharmacological safety and promising anti-inflammatory activity, resveratrol presents as an attractive compound for phase-1 clinical trials for the assessment of pharmacovigilance, pharmacokinetics and pharmacodynamics in patients with inflammatory conditions," they conclude.

"The therapeutic potential of red wine has been bottled up for thousands of years," FASEB Journal Editor-in-Chief Gerald Weissmann, MD observed, "and now that scientists have uncorked its secrets, they find that studies of how resveratrol works can lead to new treatments for life-threatening inflammation."

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