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Cynthia Kenyon, biochemist at University of California San Francisco, says it seems as if the mutant mice are “eating as much as they want, but reaping the benefits of calorie restriction,” including greater insulin sensitivity and longer lives.

The findings are puzzling to some scientists, since growth hormone was not predicted to have this effect. They aren’t yet sure how lack of growth hormone extends life, but Bartke believes it may work by improving insulin function. In the mutant mice, a lack of the growth hormone receptor made them more sensitive to insulin. Insulin sensitivity is necessary in humans to prevent metabolic diseases like diabetes. Caloric restriction also improves insulin sensitivity by lowering insulin levels.

Kenyon says that it makes sense that chemicals such as insulin – which is affected by food intake – might be the signal responsible for calorie restriction’s effects.

Molecules similar to insulin have recently been shown to affect aging and life span in many organisms. Brian Kennedy, biochemist at the University of Washington, has found that insulin-like chemicals control longevity in yeast. “There are a small number of these nutrient-responsive pathways, and calorie restriction may be going through them,” he says. And if that’s true, he adds, “the challenge for the whole field is to start working downstream,” to figure out what the signals control. Because hormones control an array of functions in the body, they make poor targets for drugs. But if scientists could isolate a more specific chemical that the hormones are targeting, they would have a better target for drugs that would mimic the benefits of calorie restriction.

Several companies, including Elixir Pharmaceuticals and Sirtris in Cambridge, MA, have been launched to hunt for chemical compounds that can extend life span, and Bartke says his study adds to evidence that insulin and its related pathways are a good place to start.

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