Research over the last decade showing that proteins called sirtuins can increase lifespan is deeply flawed, according to a new study in Nature that debunks prior claims of a direct causal link. Pioneering experiments on earthworms and fruitflies -- commonly used as models to examine the biology of human ageing -- suggested that an extra dose of the naturally-occurring enzymes could prolong life by up to 50 percent. These early results unleashed a flood of new research, much of which backed up the original findings. They also spawned a flourishing market in dubious health products claiming to boost sirtuins, and thus slow down one's biological clock. Many contained resveratrol, a molecule -- also found in red wine -- thought to activate the enzyme. But the new research, led by David Gems at the Institute of Healthy Ageing at the University College London, provides solid evidence that the supposed cause-and-effect relationship between the proteins and longer life is a mirage. Gems and colleagues reproduced benchmark studies to test whether the links might be attributable to other factors besides the allegedly miracle gene, known as Sir2 in worms and flies, and SIRT1 in mammals. "We have re-examined the key experiments linking sirtuin with longevity in animals and none seem to stand up to close scrutiny," Gem said in statement. "Sirtuins, far from being a key to longevity, appear to have nothing to do with extending life." The main problem with most of these earlier experiments was the failure to account for all the possible differences between genetically manipulated organisms and the "wild" ones against which they compared. For nematode worms, for example, once precautions were taken to ensure that the only difference between normal and test animals was the higher sirtuin levels, the added lifespan disappeared. It turned out that other mutations had occurred but escaped notice. Leonard Guarante of MIT, who conducted some of these pathbreaking studies, acknowledged in a "brief communication," also published in Nature, that his earlier work had been flawed. Gem and colleagues then reproduced similar experiments done with fruit flies, again showing that the results attributed to sirtuins were in fact due to other genetic drivers. The researchers also created synthetic fruitfly sirtuin to see if it could be activated by resveratrol, as previously claimed. But neither of two separate laboratories, using multiple techniques, could make it work. Finally, the study refutes the claim that enhanced lifespan due to dietary restriction -- itself not in doubt -- also depended on sirtuins. "Studies on yeast lifespan were the first to cast doubt on the role of sirtuins in longevity," note Carles Canto and Johan Auwerx from the Ecole Polytechnique Federale de Lausanne. The new study "puts a final nail in the coffin," they wrote in a commentary, also in Nature. But even if sirtuins are not the long hoped-for life-prolonging elixir, they may still confer important health benefits, they added. Whether directly or indirectly, the protein has been shown to protect mammals -- notably mice -- from the metabolic damage caused by high-fat diets and age-related diseases. "SIRT1 activation remains a promising approach to delaying general age-related physiological decline and to treating numerous inherited and acquired diseases," they argue. The protein may not cause an otherwise healthy animal live longer, in other words, but it could help one who over-eats to reduce related stress on its system.