New research suggests that the promising longevity gene may not lead to longer lives after all.
In recent years, studies have led some scientists to believe that the genes that make sirtuins, proteins that affect cell metabolism, could yield new targets for drugs that would extend life.
Early work in worms and fruit flies suggested that boosting sirtuins could extend life by up to 50%. Other experiments in lab animals also suggested that the proteins were responsible for the life-extending effects of calorie restriction. And even more encouraging for people, it turned out that resveratrol, a compound found in red wine, could activate the proteins.
The results were robust enough to convince some of the proteins’ earliest advocates, researchers from Harvard and Massachusetts of Institute of Technology, to found a company, Sirtis, to begin testing sirtuin-boosting agents.
But in a new report in Nature, scientists at the Institute of Health Ageing at the University College London say the foundational work connecting sirtuins to longer life in animals was flawed. The main problem, the authors write, is that the experiments didn’t take into account the effects of other genes that might have in influencing longevity. And some of these effects, they say, might differ between lab-bred animals and their naturally occurring, or ‘wild’ counterparts.
When the authors of the Nature paper, led by David Gems, reproduced the early studies in worms and flies and accounted for other genetic factors that could impact longevity, the effect of sirtuins disappeared.
The researchers also tested whether fruit fly sirtuin could be activated by resveratrol — with no luck. And they concluded that the life-extending effect of calorie restriction was not in fact due to sirtuins.
“Studies on yeast lifespan were the first to cast doubt on the role of sirtuins in longevity,” noted the authors of an accompanying commentary in Nature, reported the AFP. The new study “puts a final nail in the coffin.”
In a second paper published Nature, however, one of the discoverers of sirtuins attests that the proteins do extend life in worms, just not as much as previously thought. Reuters reported:
Leonard Guarente, a professor at the Massachusetts Institute of Technology and co-chair of the Scientific Advisory Board of Sirtris Pharmaceuticals, owned by GlaxoSmithKline, wrote that the first research on sirtuins “overestimated the extension of lifespan” in a worm with high levels of the proteins. Now, his team calculates, making a lot of sirtuins seems to increase a worm’s lifespan by about 10 to 14 percent, all else being equal.
Guarente’s group argues that sirtuins may still play an important protective role in mammals, shielding cells from the metabolic damage of daily living and safeguarding against age-related disease. He told Reuters: “I feel that the sirtuins are really the most important and actionable thing to come out of aging research, and I’m very hopeful that we will have drugs in the future based on this work to treat the major diseases of aging.”
Gems also acknowledges that the proteins may prove useful in human health in some way — potentially aiding in the development of treatments for metabolic diseases like diabetes — but that their importance in extending life may not be as strong as scientists had claimed. Researchers “got carried away” with their excitement on that front, he told Reuters.