Those sexy "fountain of youth" studies on sirtuins that grabbed headlines around the world and helped spur GlaxoSmithKline to spend $720 million to snap up Sirtris at an early development stage have once again been independently evaluated. And once again they have failed to live up to the initial hype.
Reporting in Nature, researchers repeated the experiments on sirtuins that created a clamor a few years ago, over-expressing a sirtuin gene in two animal models to see if it would prolong longevity. But they came to a radically different conclusion. It wasn't the sirtuin gene that spurred longer life in the original work, they write, but the masked mutations that were hidden in the models.
Lead investigator David Gems at the prestigious University College London says he only reluctantly stepped in to repeat a simple control process that researchers often use to double check their results on C. elegans strains used in discovery work. He mated the strain with normal nematodes, reports Nature, to rid the model of any mutations that could influence the outcome. And he concluded that "a lot of other people have wasted a lot of time" on the subject.
The original investigators, though, are refusing to budge.
"We agree there is a glitch in one of the worm strains used in the 2001 paper," MIT's Dr. Leonard Guarente tells The New York Times. "We absolutely do not agree that there is a serious question about whether sir2 extends life span in worms,"
This isn't the first time that sirtuins have been put under the microscope by researchers outside GSK. Investigators at Pfizer's Groton, CT, labs reported early last year that they also had trouble reproducing some of the original results that helped spawn fascination with the potential of sirtuins activated by resveratrol. And there's been a growing chasm between doubters and true believers. But the doubters are growing increasingly vocal that the Sirtris work was bunk.
"The field has been overfocused on overhyped claims of longevity," Johan Auwerx, an investigator at Switzerland's Federal Institute of Technology, tells Nature. "I don't think that's the main function of the sirtuins."
Sirtris was a Fierce 15 winner in 2007.