Life Extension Magazine

Life Extension Magazine August 2009

Report

Extending Life and Fighting Disease with Resveratrol

By Julius Goepp, MD

By Julius Goepp, MD

Neurodegenerative Diseases

Neurodegenerative Diseases

According to the noted Spanish neuropharmacologist Merce Pallas, “healthy aging remains one of the ideals of modern society.”52 Nowhere are the ravages of unhealthy aging more visible than in the terribly destructive neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases—and because these diseases are linked inexorably to oxidative damage and inflammation, resveratrol researchers hold high hopes for the molecule’s potential impact in these areas. It has been suggested that, like caloric restriction, resveratrol helps to preserve and regulate energy levels in brain and nerve cells, prolonging their active lives in part through beneficial, sirtuin-activating effects on mitochondria, the cellular powerhouses.41,53-56

Direct evidence of a resveratrol-mediated neuroprotective effect in Alzheimer’s disease was published in 2009 in a report by Cornell neuroscientists who studied mice given an experimental version of human Alzheimer’s.57 The mice were given resveratrol over a 45-day period; their brains were then examined for the damaging inflammatory beta-amyloid plaques characteristic of Alzheimer’s disease. Despite finding no resveratrol directly in the brain tissue, the scientists reported reductions in plaque formation of 48% to 90% in specific and important regions of the brain! These dramatic changes were accompanied by substantial increases in brain antioxidant molecules. The researchers concluded that “onset of neurodegenerative disease may be delayed or mitigated with use of dietary chemopreventive agents that protect against beta-amyloid plaque formation and oxidative stress.”

It’s not just in chronic degenerative diseases of the brain that resveratrol holds promise—neurosurgeons in Turkey found that resveratrol actually produced better biochemical outcomes in an animal model of spinal cord injury than did methylprednisolone, the steroid commonly given in high doses to trauma victims.58 And the mitochondria-preserving characteristics of resveratrol are now being explored by other neurologists and neurosurgeons as a means of preventing the devastating neurotoxic effects of restoring blood flow to brain tissue deprived of oxygen.41

Resveratrol May Reverse Arterial Aging
Resveratrol May Reverse Arterial Aging
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“Atherosclerosis is reversible” is not a phrase we expected to hear from mainstream medical researchers until very recently—since these are the precise opening words of a remarkable editorial about resveratrol that appeared in a recent issue of the prestigious New England Journal of Medicine.67 Just as astonishingly, the editorial was written by a renowned immunologist, Linda K. Curtiss, PhD, of the Scripps Research Institute in La Jolla, California. The fact that an immunologist is writing about cardiovascular disease in a trend-setting medical journal speaks volumes about how far we have come in our understanding of chronic diseases and their relationships with inflammation, which is an immune system phenomenon. What truly sets Dr. Curtiss’s article apart, though, is her description of a dramatic new phenomenon mediated by the grape polyphenol resveratrol.

Curtiss’s excitement comes from work done by Cleveland Clinic cell biologist Young-Mi Park, MD, who was exploring the role of oxidant stress and inflammation on the pathogenesis, or disease-causing mechanisms, of atherosclerosis.68 Knowing that fat-laden inflammatory cells called foam-cell macrophages trigger inflammation when they become trapped beneath the lining of blood vessels,69-72 Park’s team sought to understand why the cells become trapped, and how they could be freed from their “endothelial bondage,” thereby reversing the inflammatory process.

The most natural approach to take, Park’s group decided, was simply to test known antioxidants’ ability to prevent the foam cells from migrating into the endothelial lining in the first place, and their ability to release any cells that were already present.68 Specifically, they studied how oxidized low-density lipoprotein (LDL) promotes foam-cell formation and impairs migration. To do this they blocked LDL oxidation with several potent antioxidants. They found that oxidized LDL actually triggered production of a sort of cellular “glue” in the form of filaments of actin, one of the proteins also found in muscle tissue. The actin filaments were entangling the foam cells, preventing their natural migration out of the endothelial lining, leading to progressive inflammatory changes.

Park’s group chose resveratrol as one of the two antioxidants to test—another testimony to the respect that mainstream researchers are according this remarkable molecule (the other was N-acetylcysteine, also an antioxidant available in supplement form).68 Resveratrol treatment of the foam cells inhibited production of reactive oxygen species by greater than 90%, an important first step in breaking the cycle. Even more impressively, resveratrol partially restored the foam cells’ ability to move out of the entangling actin filaments, and migrate away from the endothelial lining!

This brings us back to Dr. Curtiss’s astounding initial observation that atherosclerosis is a reversible condition—through the use of powerful antioxidants such as resveratrol, we can now understand how oxidized LDL contributes to invasion of endothelium by inflammatory cells, and how prevention or reversal of LDL oxidation promotes mobilization of inflammatory cells and their emigration away from vessel linings.

As Dr. Park concluded, “[these studies] also provide additional mechanistic support for the atheroprotective effect of antioxidants.”68 Resveratrol is already well-known as a cardiovascular protective supplement—the work of Park and others is now showing us that resveratrol must also be considered a valuable cardiovascular therapeutic supplement, one that can literally “turn back the clock” on chronic vascular diseases of aging!

Cancer

Cancer is one of the most-feared scourges of humanity, and the risk of cancer increases progressively with advancing age. It is only in the past three years that significant attention has been paid by oncologists to the chemopreventive capacity of resveratrol—but that omission is being rapidly remedied through an outpouring of new research. Roman biologists have discovered, for example, that the most active form of the molecule, trans-resveratrol, causes human breast cancer cells in culture to commit the orderly suicide referred to as apoptosis, one of the most important and effective means of treating cancers and of preventing their progression.59 Scientists at the University of Nebraska Medical Center even found that they could utilize resveratrol to prevent damage to DNA caused by excess estrogen, effectively preventing the initiation of some breast cancers.60

Cancer

Because resveratrol acts by so many different mechanisms, it represents a true “multiple-prong” approach to prevention and treatment of cancers. These effects are especially notable in tissues with a high rate of natural cell turnover, where carcinogens can rapidly corrupt the DNA code and induce tumors—tissues such as the gastrointestinal tract and the skin. Oncologists at the Northeastern Ohio Universities Colleges of Medicine and Pharmacy in Ohio, for example, found that they could use resveratrol to inhibit liver cancer cells from proliferating, and cause them to undergo death by apoptosis, ultimately reducing the size and number of liver tumors in rats given a potent carcinogen.61

A more profound understanding of resveratrol’s role in toxin-induced cancers (typical of the gastrointestinal tract and skin) has been revealed just this year, by Italian toxicologists studying the powerful enzyme systems involved in carcinogenesis.62 Remarkably, they have demonstrated that resveratrol inhibits the actions of certain “bioactivating” enzymes that inadvertently convert minor toxins into major carcinogens, and at the same time promotes activity of detoxifying enzymes that help prevent conversion of normal cells into cancerous tumors.

Indian toxicology experts also found that resveratrol prevented cancerous changes—this time in a rat model of skin cancer.63 Using resveratrol, they could delay the onset of tumor development, reduce the total number of tumors, and reduce tumor size in the skin of rats treated with a potent carcinogen. The scientists concluded that resveratrol regulates apoptosis and cell survival in mouse skin tumors and deserves consideration as a potent chemopreventive agent.

Finally, also early in 2009, another group of Indian scientists reported that they could block toxin-induced colon cancers in rats by supplementing them with resveratrol before exposing them to a deadly carcinogen.64 Like the preceding group, they found reductions in both the occurrence rate and the size of tumors; importantly, both benign and malignant tumor types were suppressed. Though we are midway through 2009, a host of other new studies have already appeared, confirming and extending findings about resveratrol’s astonishing chemopreventive capabilities.41,65

Summary

Summary

The plant-derived polyphenol resveratrol, and especially its highly active form, trans-resveratrol,5,59,66 have been making big news in recent days. We’ve long known that resveratrol has potent antioxidant and anti-inflammatory effects, making it a key item in our armamentarium of supplements that can prevent age-associated chronic illness. The real news is that resveratrol continues to be linked to the life-extending effects of the powerful sirtuin molecules that control the fundamental processes associated with aging itself. By potently activating sirtuins, resveratrol stabilizes DNA to prevent cancerous changes, switches on antioxidant and anti-inflammatory defense mechanisms native to cells, and even instructs certain cells to commit organized suicide by apoptosis. The end result is an almost incredible array of health benefits, from reduction in cardiovascular risk factors to protection against neurodegenerative disease to cancer prevention. Indeed, resveratrol is being actively explored now by big pharmaceutical companies eager to cash in on its potency by creating new drugs derived from the natural molecule. But there’s no need to wait, because highly purified forms of trans-resveratrol are already available, waiting to provide their beneficial effects immediately.

If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.

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