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Geneticists Claim Ageing Breakthrough but Immortality Will Have to Wait
Ian Sample, The Guardian
November 18, 2005
A genetic experiment to unlock the secrets of the ageing process has created organisms that live six times their usual lifespan, raising hopes that it might be possible to slow ageing in humans.
The geneticists behind the study say the increase in lifespan is so striking, they may have tapped into one of the most fundamental mechanisms that controls the rate at which living creatures age.
The tests were carried out in single-celled organisms, forcing them into what the researchers refer to as an "extreme survival mode". Instead of growing quickly and showing signs of ageing, the organisms became resilient to damage and were better able to repair the genetic defects that build up with age, often leading to cancer in later life.
"When you do this genetic manipulation, you can get some of the longest lifespans ever described," said Valter Longo, a biomedical gerontologist at the University of Southern California. "We have good reason to believe this genetic effect is conserved in other organisms. We're working with mice and human cells now and are already starting to see the same response."
A large body of research has already shown that severely restricting diet can boost the lifespan of flies, worms and mice by around 40%. Scientists believe that drastically cutting calories triggers a switch in an organism's behaviour, from growing and being able to reproduce, to a state of stasis in which growth and ageing are put on hold at the expense of reproductive capability, until more food is available. Scientists are now trying to mimic the effect by tinkering with genes in the hope of developing anti-ageing treatments that work without having to cut food intake.
"We're not too far from being able to exploit this understanding to at least start thinking about drugs that can put humans in an anti-ageing mode. That doesn't mean we'll necessarily live six times longer, but it means we could slow down the DNA damage we accumulate as we age, and that could protect us from cancer," said Dr Longo.
In the experiment, Dr Longo's team took yeast cells and knocked out two key genes, named Sir2 and SCH9. The latter governs the cells' ability to convert nutrients into energy. They found that instead of dying after a week, the cells lived for up to six weeks. Dr Longo said parallel experiments on human liver cells appeared to replicate the effect, but refused to elaborate until the results have been published.
The researchers believe that the Sir2 gene normally plays a role in restricting an organism's lifespan, and allows energy from the food it eats to be directed into growth and reproduction. By blocking the gene, the cells were essentially tricked into believing food was scarce and switched them into a survival mode.
"When you start increasing lifespan by five or six times, it means you're really playing with the life and death programmes of organisms. We're telling the organisms to go into a completely different mode of slow ageing," said Dr Longo. "What they're doing is saying 'I cannot afford to age. I still have to generate offspring, but I don't have enough food to do it now.' "
Research has now begun to test whether the effect works in mice. According to Dr Longo, lab mice bred with the equivalent gene knocked out appear to live longer, but are smaller, infertile and often suffer muscular defects, suggesting the gene is necessary for normal foetal development.
The research is a big step in a small field that has been progressing at pace since the advent of the new tools of genetics. Another paper published today in the US journal Science describes the discovery of 10 new genes that are thought to regulate longevity in yeast cells. "Even though yeast is a simple, single-cell organism, it's still capable of revealing mechanisms in the ageing process," said the study's lead researcher, Stanley Field of the University of Washington in Seattle.
According to Dr Longo, studies in animals are likely to continue for the next 10 years before tests in humans. If the same genetic mechanisms prove to exist in humans, he believes it could lead to drugs that suppress ageing, particularly after people have had families.
Were drugs to become available that dramatically extended lifespan, the social impact of a population boom could have serious consequences for homes and pension provision.
Aubrey de Grey, a biomedical gerontologist at Cambridge University and advocate for therapies that greatly extend life, believes that while the problems should not be underestimated, it is unethical not to pursue anti-ageing research.
"A remarkably high proportion of people seem to like living in cities. With the staggering amounts of wealth that will be freed up by not having any frail people around any more, it will become practical to build very high-quality urban accommodation for everyone, and the density of that accommodation is such that a population of at least 20 billion will hardly encroach at all on the amount of rural space that currently exists," he said.
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