For years, researchers who study aging have pursued a dream: a way to mimic the effects of extending the life of calorie restriction without drastic diet. It was ten years ago, a group claimed that artificially stimulate the activity of a gene offered a way to do it. Now a new paper throws cold water on this claim, adding to doubts that the influence of genes celebrated the life of all.
Scientists who study aging have long been a reliable way to increase lifespan in many animals: starve yourself. Animals that eat about 30% to 50% less calories than normal live 30% longer, or even more. But how calorie restriction extend life? There are about ten years, a research team suggested that in worms, the response was a gene called SIR2 . The idea was that cutting calories boosted production of its protein gene and that this extended life in turn. Indeed, this group increased the expression of SIR2 by artificial means (without stopping to eat) and extended their lifespan. It was not a great leap to start wondering if scientists could develop a pill to support production of the SIR2 protein, allowing people to live much longer and in better health than we do now without hunger. And in fact, companies are already testing drugs that stimulate the production of one of the parents of SIR2 family of proteins called sirtuins are-in people to treat diseases associated with age such as type 2 diabetes
But in the past year, a handful of studies have questioned whether SIR2 and genes encoding other sirtuins really help explain why caloric restriction slows aging.
The new study, published online today in Nature , amplifies doubts, suggesting that SIR2 does not do much at all to extend the life in verse and flies. David Gems, a biogerontologist at University College London and lead author of the study, said he began to reconsider SIR2 when he was working with genetically modified to produce extra for SIR2 protein. But then someone in the laboratory Gems coupled worms several times with a normal strain, "and longevity is gone," Gems said, although the offspring was still SIR2 modified gene.
it is difficult to produce large groups of genetically identical worms and flies, so it may be difficult for scientists to tell whether a genetically modified strain act differently than to control or flies because of his DNA damage or because the two groups of animals other genetic variations. Normally, researchers move it by their mating strain genetically modified several times with a stress control a strategy called "outcrossing . "Outcrossing irons out differences between the genetically modified strain and the control group by the more genetically uniform pair.
following the initial observation of his laboratory that SIR2 lifetime effect could disappear in the worms by crossing Gems teamed with Matt Kaeberlein at the University of Washington, Seattle, and Linda Partridge of University College London, who both previously questioned the role of sirtuins in aging. With other colleagues, they took both worms and flies genetically altered to make additional SIR2. The worms were crossing by up to six times more than the other groups had generally done in the past. The offspring lived spans yourself from normal life if they were still producing additional SIR2 protein. In parallel, the group Partridge found that overexpression of SIR2 in flies did not increase their lifespan, either.
"In terms of aging and dietary restriction," said Gems SIR2 and related genes are probably "completely irrelevant. ... We tried so hard to see effects at all in many different settings and we have not seen. "
not so fast, say SIR2 donors. Leonard Guarente of the Massachusetts Institute of Technology in Cambridge, who a decade ago found a SIR2-lifetime connection, does admit that the original worm paper was an error: In the same issue of Nature that the study of gems, he published a short article noting that unwittingly worms get a second genetic mutation, in a gene called Dyf . This mutation, it appeared, also helped to live longer. When they had only additional SIR2 , they lived between 10% and 15% longer than normal, Guarente found, not the 30% originally reported. "We had a bad thing in our study," he said. "We tried to set the record straight, and we have."
But this does not mean that SIR2 not about the life, he argues, especially in light of important work in the field who has repeatedly linked SIR2 for a lifetime and calorie restriction. " say at this late date that sirtuins do not regulate aging, with thousands of published sirtuins, is like saying the Earth is flat, "says Guarente from the study of precious stones, he notes." You can always get an experience not to work. "
One reason for different results is that aging is difficult to study in worms and flies, says Scott Pletcher, a geneticist at the University of Michigan, Ann Arbor. "If we measure 10%, 20% of the differences in lifespan, which may depend on the fact that the temperature is warmer, there is enough food. We really control all these things. It is a challenge. " For now, Pletcher is on the fence about what exactly do sirtuins. "Some voices were given [by the Gems paper] to what was floating in the community for some time," Pletcher said, which is "that there is some uncertainty around these initial results."
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