“If people should look at the sirtuin literature as a whole, they will come to the conclusion that sirtuins are the most actionable mechanisms for developing drugs to mitigate the diseases of aging,” says Guarente.
David Sinclair, a biologist at Harvard and former collaborator of Guarente’s, dismisses Gems’s interpretation. “The group that published the paper that contradicts the Guarente lab has repeatedly produced data that attacks other groups; this is just another one of those,” says Sinclair. “When I look at the Guarente data, I remain convinced that sirtuins extend lifespan. The debate seems to be over how big the effect is.”
Sinclair has bet big on sirtuins, founding a startup called Sirtris whose premise is that activating the proteins produced by these genes with drugs will help combat such diseases of aging as diabetes, heart disease, and cancer. (Pharmaceutical giant GlaxoSmithKline acquired Sirtris for $270 million in 2008.)
Sinclair had previously discovered that resveratrol—a molecule found in red wine—could activate proteins produced by the sirtuin genes, and his team developed a number of compounds designed to activate sirtuins more powerfully. (In another branch of the debate, some studies have questioned whether resveratrol truly activates sirtuins or whether it acts through its effect on other proteins.)
In practical terms, how much does this argument really matter? The ultimate goal of aging research is to figure out how to improve human health. And drug development efforts that have emerged from the sirtuin research still look encouraging.
Last year, researchers at the National Institute on Aging showed that one sirtuin compound, called SRT-1720, improves health and longevity in mice fed a high-fat diet. Treated fat mice lived more than 40 percent longer than untreated fat mice, though both died sooner than their lean counterparts. The drug did not appear to increase the maximal lifespan of the obese animals.
“I don’t think you need to convince people they are longevity drugs,” says Johan Auwerx, a researcher at the Ecole Polytechnique Federale de Lausanne, in Switzerland, who wrote a commentary accompanying the papers in Nature. “They do control health span, so I still think they are very interesting pharmaceutical targets. Who wants to live forever? You want to live well.”