Other scientists agree that the work is exciting, but they caution that it’s not yet clear what role the enzymes play in aging or in the effects of caloric restriction. “People have made arguments that NAD level is important, but at this point, it’s one of a lot of players,” says David Finkelstein, a biologist at the National Institute on Aging.
Additional studies are needed to truly assess the role of these enzymes, says Matt Kaeberlein, a biologist at the University of Washington. “These enzymes could potentially be important regulators of disease and potentially useful drug targets, but we need to get into animal models to find out how important they are,” he says. Most of the current research was limited to cell lines, but Sinclair and his colleagues are now studying a mouse that overexpresses the mitochondrial enzyme. “If the mice are long-lived and show resistance to age-related disease, that will support this hypothesis,” says Kaeberlein.
Sirtris CEO and cofounder Christopher Westphal says that the company, which is already running clinical trials of a potential anti-diabetes molecule that targets SIRT1, is screening for compounds that target a number of the sirtuins. But Westphal won’t say if the company has identified specific compounds that target SIRT3 and SIRT4. “SIRT3 and SIRT4 also look like they would be interesting for diabetes,” says Westphal. “Maybe they would treat it in a different way than SIRT1.”