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Scientists have long known that a very low-calorie diet can increase life span in organisms as diverse as yeast, flies and mice. One of the most puzzling questions in aging research, however, is how it works. If they can figure out the molecular processes underlying the boost in longevity, scientists think they might be able to harness the life-extending benefits without restricting diet.

A new study offers evidence that a decline in growth hormone and a corresponding boost in sensitivity to insulin may be the reason why mice live longer when they eat less – and that those two hormones may be critically important in controlling aging and longevity.

The study opens up new questions about the role of growth hormone in aging. In humans, growth-hormone levels decline with age, and artificial growth hormone has been touted as an anti-aging drug. But at least in mice, high levels of growth hormone reduce life span, says Andrzej Bartke, a physiologist at Southern Illinois University School of Medicine, who led the study. And these results suggest that lowering growth hormone in mice can mimic the benefits of calorie restriction without the diet.

Within the last few years, biologists have found that mutating certain genes in lower organisms can make them live longer. These discoveries helped fuel the idea that life span is directly controlled by a genetic program in the body – a program that scientists may be able to manipulate. But, so far, none of these genes have explained the remarkable effects of calorie restriction.

The current study, published in the May 16 Proceedings of the National Academy of Sciences, examined a line of mice who was resistant to growth hormone, which promotes childhood growth and has several other functions in the body. These mice, who are smaller than normal, lack the growth hormone receptor, a molecule that sits at the surface of cells and binds to growth hormone circulating in the blood. Without the receptor, the body’s tissues are deaf to the hormone’s signal.

Scientists have previously shown that caloric restriction can increase life span in mice by 25 to 30 percent. In the new study, the researchers found that mutant mice, which lack the growth hormone receptor, live just as long as caloric-restricted mice – even though they ate a normal amount of food. The results suggest that lack of growth hormone triggers a molecular reaction similar to caloric restriction.

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