What a year it has been for resveratrol, the polyphenol molecule from red wine. Last year at this time it was the toast of the town, having been credited with triggering a metabolic change leading to increased lifespan in experimental models, then catapulted into the limelight as a potential cancer cure with clinical trials under the auspices of pharma giant GlaxoSmithKline. Sales of resveratrol supplements were skyrocketing, with audacious claims about weight loss, brain power, and longevity, never mind that none of this had been proven in humans. But with the new year came new controversy. Two of Glaxo’s competitors, Pfizer and Amgen, published their own studies on resveratrol, concluding that the longevity effect was false, an artifact of the testing method. What few clinical trials there are in humans revealed that it is poorly absorbed and doesn’t last very long in the body anyway. Then in November Glaxo abruptly announced the suspension of the clinical trial and all further development of their flagship resveratrol derivative, SRT501. Supplement sellers started to look more and more like snake oil peddlers, while enthusiasm began to fade in the scientific community.
Despite these setbacks, progress on the basic science front continues to reveal interesting properties of resveratrol. One line of research looks at extending lifespan of cells not through metabolic change but by repairing the caps on DNA strands that are clipped each time the cell divides. These caps, called telomeres, are sequences on the ends of the chromosomes that prevent unraveling with the replication cycle; with each division they shorten, limiting the number of times the cycle can repeat and therefore the lifespan of the cell. Cell types that require constant replenishment, such as skin and the linings of blood vessels, show their age more than others as they lose the ability to replicate. But cancer cells have figured out how to by pass this limitation and become immortal by rebuilding telomeres with an enzyme called telomerase. Control telomerase and you harness cellular immortality, and it appears resveratrol may provide the key.
The source of new cells is what are called progenitor cells, which in turn trace their lineage to stem cells. A recent study enticingly called “Immortalization of epithelial progenitor cells mediated by resveratrol” outlines the mechanism by which resveratrol pulls this off in skin cells. There is a lot that remains to be deciphered about this but it looks promising. Another paper reported on the role of resveratrol in reducing senescence of the progenitor cells that replace blood vessel lining, an important step in countering atherosclerosis, by activating telomerase. Just as important though is that resveratrol uses the same metabolic pathways to slow the growth of cancer cells.
Such is the state of affairs with resveratrol: exciting new findings on the leading edge of biomedical research, while verification of its use in clinical medicine seems ever farther off. All I can say is stay tuned.
1. Pearce VP, Sherrell J, Lou Z, Kopelovich L, Wright WE, Shay JW. Immortalization of epithelial progenitor cells mediated by resveratrol. Oncogene 2008 Apr 10;27(17):2365-74.
2. Xia L, Wang XX, Hu XS, Guo XG et al. Resveratrol reduces progenitor endothelial cells senescence through activation of telomerase activity by Akt-dependent mechanisms. Br J Pharmacol 2008 Oct;155(3):387-94.
3. Lanzilli G, Fuggetta MP, Tricarico M, Cottarelli A et al. Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro. Int J Oncol 2006 Mar;28(3):641-8.
4. Fuggetta MP, Lanzilli G, Tricarico M, Cottarelli A et al. Effect of resveratrol on proliferation and telomrease activity of human colon cancer cells in vitro. J Exp Clin Cancer Res 2006 Jun;25(2):189-93.