Can drugs that supposedly “activate” a controversial target—sirtuin proteins—stop or even reverse the aging process? A new report this week said “No.” According to this report, published Wednesday night in Nature, sirtuin activators do not extend lifespan in roundworms and flies and earlier studies that said they did were flawed. Nonetheless, GlaxoSmithKline (GSK) continues to invest hundreds of millions of dollars into developing drugs to hit these targets—more about their findings below—and if the drugs work, for whatever reason, the scientific squabbles will not matter.
I recently had the chance to hear Harvard professor David Sinclair talk publicly about his and GSK’s research into sirtuin activators. Sinclair was the scientific founder of Sirtris and he reported at a forum on longevity in Cambridge, MA, that GSK has high hopes of near-term confirmation in mice that some sirtuin activators do extend lifespan. Based on its continued investment, GSK still believes that the $720 million acquisition of Sirtris in 2008 was a smart one.
The Nature report, just the latest in a series of publications that question the sirtuin-longevity link, will be even tougher for Sinclair and other sirtuin researchers to overcome. The new research reported that sirtuin proteins, when overexpressed in nematode worms and fruit flies, do not actually have an effect on longevity. This directly contradicts the original publications linking Sir2 and other sirtuins with increased lifespan. The new report further goes on to contradict the landmark 2006 paper, also published in Nature, in which Harvard researchers led by Sinclair reported that mice fed resveratrol which, they demonstrated using expression analysis, activated sirtuins, live on average 20 percent longer and in some cases much longer than that.
The same researchers, both at University College London, went on the record as sirtuin skeptics in 2007. David Gems and Linda Partridge then set out to prove their claim that the original sirtuin and resveratrol findings, which led to the founding and eventual acquisition of Sirtris, were irreparably flawed. Building on earlier reports that the round worms used in the original studies carried a gene that control organisms did not carry, and that it was this gene that predisposed the worms to live longer, Gems and Partridge showed in this paper that organisms identical to one another except for the expression level of sirtuins could not be made to live longer.
Sirtuin research is nothing if not contentious. Apparently eager to fan the flames, Nature in the same issue this week published a rebuttal from Leonard Guarente, the author
