Extending Healthy Lifespans? A Pill on the Horizon?

Resveratrol, the much-hyped ingredient found in red wine and sold widely as a nutritional supplement, is known to improve the health and extend the lifespan of mice. Can it do the same for humans? Without nasty side effects? And at what dose?

A study published today in Cell Metabolism helps unravel a few more of resveratrol’s mysteries. In particular, researchers have shed new light on how resveratrol works. Key to its effectiveness is a gene known as SIRT1, found in slightly different forms in species as different as yeast and humans. SIRT1 plays many roles, some tied to core metabolic processes. The new study shows that in mice, even a low dose of resveratrol interacts with SIRT1 to improve metabolism.

What makes this study especially interesting is that researchers had to create a special strain of mice in order to test whether SIRT1 is necessary for resveratrol to work. If mice have no SIRT1, they do not develop properly. So two graduate students, Nathan Price and Ana Gomes, developed a novel strain of mice with an unusual copy of the SIRT1 gene, one that could be switched off at adulthood.

By administering a drug (tamoxifen), researchers can “induce” or switch the SIRT1 gene on and off, a strategy that will likely be used in other studies. "This is a drug inducible, whole body deletion of a gene," David Sinclair, the study's senior author, said in a press release from Harvard Medical School. "This is something that's rarely been done so efficiently. Moving forward, this mouse model will be valuable to many different labs for other areas of research."

Photo by R. Cole-Turner

In this case, the switchable SIRT1 mouse provided proof that SIRT1 is key to resveratrol’s effectiveness. Why is that important? Because resveratrol is a complex molecule that interacts with the body in many unknown ways. While it may be beneficial, it may have unwanted side effects. So researchers are trying to design a more simple molecule that provides the benefits of resveratrol without all the risks. One strategy is to boost SIRT1 activity. By proving that SIRT1 is involved, this study provides support for that strategy, which is already being pursued by pharmaceutical firms.

"The results were surprisingly clear," said. "Without the mitochondria-boosting gene SIRT1, resveratrol does not work."

Are we any nearer a magic pill that slows aging or promotes longevity? Perhaps. The headline of the press release from the publisher, Cell Press, claims that this work “restores hope for anti-aging pill.” Remember, of course, that the work reported here is entirely with mice.

Even so, the paper itself concludes with this statement: “This model supports the enticing possibility of designing and developing potent small molecules that provide the health benefits of resveratrol by activating SIRT1 and downstream pathways to treat metabolic and other age-related diseases.”

The treatment of age-related diseases, including diabetes, is a huge target for pharmaceutical firms. But beyond that lies that even bigger market for human enhancement, specifically for enhancing the span of healthy decades.

The study, "SIRT1 Is Required for AMPK Activation and the Beneficial Effects of Resveratrol on Mitochondrial Function," appears in the May 1, 2012 issue of Cell Metabolism.