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Resveratrol Extends Cell Survival and Life Span

January 2004

Rodents, worms, flies, and yeast cells live longer when fed a low-calorie diet, which protects mammals against age-related diseases, including cancer. In May, researchers reported the first known genetic link between environmental stress and a longer life span in yeast.*

Triggered by salt, heat, or caloric restriction, a yeast “longevity gene” was found to stimulate the activity of Sir2, an enzyme that belongs to the sirtuin family of enzymes known to extend the life span of yeast and worms.

Now, a group from Pennsylva-nia’s Biomol Research Laboratories has found a way to duplicate the benefits of caloric restriction in yeast cells by polyphenols, antioxidants that are found in vegetables, olive oil, fruit, and wine, and whose levels in plants increase in response to stress. The findings, reported in August in the journal Nature’s advanced online edition, show that polyphenols prompt yeast cells and human cells to prepare for harsh conditions by switching to a life-extending survival program that mimics caloric restriction. This occurs by a mechanism other than their antioxidant action—activation of the sirtuin family, the SIRT2 protein in yeast and SIRT1 protein in humans.

The most potent activator of sirtuins is resveratrol, found in grapes, wine, and peanuts. In yeast, resveratrol mimics caloric restriction by stimulating the SIRT2 enzyme, increasing the stability of DNA, and extending the life span of the yeast cells by 70%.

In experiments with human cells, resveratrol activated a similar pathway that enabled 30% of the cells to survive exposure to radiation, compared to 10% of untreated cells. Little is known about the human SIRT2, except that it switches off p53, a growth-regulating protein that plays a role in programmed cell death. Increasing survival through the activation of SIRT1 and SIRT2 by polyphenols may allow cells time to repair damage, thereby extending their life span.

—Carmia Borek, PhD

* Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae life span. Nature. 2003 Sep 11;425(6954):191-6. Epub 2003 Aug 24.

Ginkgo Biloba May Slow Glaucoma’s Progression

A small study of patients with normal tension glaucoma indicates that ginkgo biloba may slow the progression of the disease.

Glaucoma is an eye disease in which damage to the optic nerve leads to progressive peripheral vision loss. This loss can be measured with specialized visual field testing. In most glaucoma cases, the pressure inside the eye (intraocular pressure) is elevated; in people with “normal tension glaucoma,” how-ever, optic nerve damage occurs despite normal intraocular pressures.

In an effort to determine whether ginkgo biloba affects visual field loss in patients with normal tension glaucoma, Italian researchers recruited 27 patients with visual field loss from normal tension glaucoma and divided them into two groups.* The first group received 40 mg of ginkgo biloba extract in pill form three times a day for four weeks, followed by a washout period of eight weeks, and then four weeks of placebo treatment comprising similar-appearing pills that did not contain ginkgo biloba. The second group received the placebo pills first, and then the ginkgo biloba extract after the washout period. On average, patients performed significantly better in visual field testing after receiving the ginkgo biloba extract than after receiving the placebo.

“Our results suggest that ginkgo biloba extract can effect an improvement in preexisting visual field damage in some individuals with normal tension glaucoma,” the researchers wrote in their article published in the journal Ophthalmology.

“Ginkgo biloba extract has numerous properties that theoretically should be beneficial in treating non-intraocular pressure-dependent mechanisms in glaucoma. Its multiple beneficial effects, including increased ocular blood flow, and its antioxidant activity, platelet activating factor inhibition, nitric oxide inhibition, and neuroprotective activity combine to suggest that ginkgo biloba extract could play a major role in the treatment of glaucoma.”

—Marc Ellman, MD

* Quaranta L, Bettelli S, Uva MG, Semeraro F, Turano R, Gandolfo E. Effect of ginkgo bilo- ba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology 2003 Feb;110(2):359-62; discussion 362-4.

Broccoli May Be Tops in Health-Promoting Benefits

Cruciferous vegetables such as cauliflower, brussels sprouts, cabbage, and kale are powerful anti-cancer agents, but among this group, broccoli may contain the most life-extending nutrients. Rich in vitamins and fiber, broccoli also boasts special ingredients that promote good health and prevent disease.

Broccoli is unusually rich in phytochemicals that fight cancer, including indoles, isothiocyanates, and glucoraphanin, which the body converts to sulforaphane. These substances can prevent carcinogens from damaging cell DNA and causing various forms of cancer.

Indoles can reduce the risk of breast cancer by stimulating enzymes that weaken the female hormone estrogen. Isothiocyanates, which are up to 100% higher in young broccoli sprouts than in adult broccoli stalks,1 stimulate glutathione S-transferase and other enzymes that prevent carcinogens from entering the cells. And sulforaphane can stimulate the production of phase II enzymes that are powerful carcinogen detoxifiers.

Since 1992, pharmacology professor Paul Talalay and his group at Johns Hopkins University have been studying broccoli’s cancer-fighting properties. Their research has demonstrated that sulforaphane can prevent breast and colon cancer in mice and also destroy Helicobacter pylori, the bacteria linked to gastritis, stomach ulcers, and stomach cancer (the second most common form of cancer).2

Containing generous amounts of such vital nutrients as calcium, manganese, beta carotene, vitamin C, and vitamin K, broccoli’s health benefits are undiminished by cooking; in fact, heat actually appears to increase indoles in broccoli.

An average serving of cooked broccoli has more vitamin C than an orange and as much calcium as an eight-ounce glass of milk, while an average broccoli spear has three times the fiber of a slice of wheat bread. Broccoli sprouts have as much glucoraphanin as a pound and a quarter of cooked broccoli. Those looking for a vegetable packed with essential nutrients and life-extending components may want to reach first for the broccoli.

—Donna Caruso


1. Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci U.S.A. 1997 Sep; 94(19):10367-72.

2. Fahey JW, Haristoy X, Dolan PM, et al. Sulforaphane inhibits extracellular, intracel- lular, and antibiotic resistant strains of heli- cobacter pylori and prevents benzo[a]pyrene- induced stomach tumors. Proc Natl Acad Sci U.S.A. 2002 May 28;99(11):7610-5