DNC News

Resveratrol lengthens yeast lifespan

Jacob Schor, ND

Fall, 2004


Subject: Resveratrol, a compound we suggest for use in cancer treatment, significantly increases lifespan.

(in small print, we might add that at this point, research has only shown that it does this in baker's yeast and fruit flies, but it's the thought that counts)

I've written about resveratrol on a regular basis over the last four or five years.  Resveratrol is a chemical extracted from grapes initially to see if it was the 'magic bullet' to protect people against heart disease.  A notable side effect was noticed in the late 1990's.   Resveratrol stimulates cancer cells to self destruct or in fancy words undergo apoptosis.  In the articles written about this compound there is no debate about whether it works, the debate has been on how and why it works.

An interesting article was published in Nature August 24, 2003 looking at the effect Resveratrol has on baker's yeast.  Resveratrol fed to yeast lengthens their lifespan by about 70%. It also lengthens the lifespan of fruit flies by about 25%.   What is interesting is how it does it.   Resveratrol stimulates the yeast cells to produce a class of chemicals called sirtuins.  These are the same chemicals which are stimulated by caloric restriction.  Caloric restriction is the most potent anti-cancer, life span increasing intervention that has ever been studied.   We don't talk about it much. In a free living population (such as people, not rats living in cages, where you can not control what and how much they eat), caloric restriction is next to impossible to do.  This is the sort of thing we've always joked wouldn't be useful until we could put it in a pill.   Perhaps now we can.

I will paste in both the Science News review article and an abstract of the Nature study for you to read if interested.

Science News:
Red wine ingredient makes yeast live longer
Baker's bug hints at health benefit of plant compounds.
26 August 2003
Helen R. Pilcher


An ingredient of red wine extends lifespan by up to 70% - in yeast[1]. The compound seems to mimic the age-enhancing effects of calorie restriction on the single-celled organism.

Capitalizing on the chemical, called resveratrol, is a long way off in humans, says David Sinclair of Harvard Medical School in Boston , Massachusetts , who led the research. To match the yeast doses, he says, humans would need to drink a glass of their favorite vintage morning, noon and night.

But the research may help explain why red-quaffing Mediterraneans live to a ripe old age. Resveratrol boosts levels of an enzyme called Sir2, which is thought to extend lifespan by stabilizing DNA. "It's highly plausible that boosting enzyme activity will slow functional decline in old age," agrees Peter Piper, who studies ageing at University College London.

Resveratrol is one of a group of chemicals called polyphenols. Previous research has suggested that these can protect against heart disease and osteoporosis in humans. "It may not be just a longer life - it may also be a healthier one," says Sinclair.

The compound is one of 17 plant molecules so far found to extend life in baker's yeast (Saccharomyces cerevisiae). Resveratrol also gives fruitflies, which typically live for around a month, an extra ten days of life, says Sinclair. Studies on mice are in the pipeline.

Sinclair gave his yeast fresh grape extract. Normally, the organism divides around 25 times and then dies. Resveratrol-treated yeast underwent an extra 15 replications.

Many polyphenols are also found in tea, fruit and vegetables, says Piper. "It stresses the importance of eating a healthy, balanced diet," he says. Pharmacologists are also developing a stable, slow-release resveratrol pill.


References
Howitz, K. T. Small molecule activators of sirtuins extend Saccharamyces cerevisiae lifespan. Nature, published online, doi:10.1038/nature01960 (2003).

© Nature News Service / Macmillan Magazines Ltd 2003


Nature AOP, published online 24 August 2003; doi:10.1038/nature01960

Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan

KONRAD T. HOWITZ1, KEVIN J. BITTERMAN2, HAIM Y. COHEN2, DUDLEY W. LAMMING2, SIVA LAVU2, JASON G. WOOD2, ROBERT E. ZIPKIN1, PHUONG CHUNG1, ANNE KISIELEWSKI1, LI-LI ZHANG1, BRANDY SCHERER1 & DAVID A. SINCLAIR2

1 BIOMOL Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, Pennsylvania 19462, USA
2 Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Masachusetts 02115, USA

Correspondence and requests for materials should be addressed to D.S. (david_sinclair@hms.harvard.edu).

In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD+-dependent protein deacetylases. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor. Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible
evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators.

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© 2003 Nature Publishing Group



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