Eat more, weigh less, live longer? 19:00 23 January 03 NewScientist.com news service
Clever genetic detective work may have pinpointed the reason why a near-starvation diet prolongs the life of many animals.
Ronald Kahn at Harvard Medical School in Boston, US, and his colleagues have been able to extend the lifespan of mice by 18 per cent by blocking the rodent's accumulation of fat in specific cells. This suggests that leanness - and not necessarily diet - promotes longevity in "calorie restricted" animals.
"It's very cool work," says aging researcher Cynthia Kenyon of the University of California, San Francisco. "These mice eat all they want, lose weight and live longer. It's like heaven."
Calorie restriction dramatically extends the lifespan of organisms as different as yeast, worms and rodents. Whether this works in humans is still unknown, partly because few people are willing to submit to such a gruelling diet.
But many researchers hope they will be able to trigger the same effect with a drug once they understand how less food leads to a longer life. One theory is that eating less reduces the accumulation of harmful chemical by-products called free radicals that can damage cells. But Kahn's team wondered whether the animals simply benefit by becoming lean.
Obesity protection
To find out, they used molecular biology tricks to disrupt the insulin receptor gene in lab mice - but only in their fat cells. "Since insulin is needed to help fat cells store fat, these animals had less fat and were protected against obesity," explains Kahn.
This slight genetic change in a single tissue had dramatic effects. By three months of age, Kahn's modified mice had up to 70 per cent less body fat than normal control mice, despite the fact that they ate 55 per cent more food per gram of body weight.
In addition, their lifespan increased. The average control mouse lived 753 days, while the lean and mean rodents averaged a lifespan of 887 days. After three years, all the control mice had died, but one-quarter of the modified rodents were still alive.
"That they get these effects by just manipulating the fat cells is provocative," says Leonard Guarente of the Massachusetts Institute of Technology, who studies calorie restriction and aging in yeast.
But Guarente says Kahn has yet to prove that the same effect is responsible for increased lifespan in calorie-restricted animals. "It might be the same effect or there might be two routes to longevity," he points out, "and that would be very interesting."
Journal reference: Science (vol 299, p 572)
Philip Cohen