By Dr Ananya Mandal, MD
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.
Till date researchers have worked on experiments on earthworms and fruitflies - commonly used as models to examine the biology of human ageing and 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.
However 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…Sirtuins, far from being a key to longevity, appear to have nothing to do with extending life,” Gems said.
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. Gems 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.