A number of studies have shown that restricting calories increases the lifespan of animals, but the biological basis for this has remained elusive. A new report hints that growth hormone, as well as insulin, are key factors in the life-extending effects of calorie restriction.

"The implication ... for pharmaceutical development would be that the signaling pathways of growth hormone and insulin may be logical targets for development of anti-aging medicine," Dr. Andrezej Bartke from Southern Illinois University in Springfield stated.

"Although it would be irresponsible to recommend that healthy people start using anti-diabetic drugs," said Bartke, "it is reasonable to suggest that treatment(s) causing an improvement in insulin sensitivity combined with modest reduction in insulin release would reduce risk of age-related disease and likely also delay aging."

Bartke's team tested whether growth hormone and insulin are tied to the life-extending effects of calorie restriction in a series of experiments with normal mice and mutant mice deficient in growth hormone.

The mutant mice do not express the receptor for growth hormone (and are therefore growth hormone resistant), have profoundly suppressed insulin levels, and are known to live longer and age more slowly than normal mice, the researchers note in Proceedings of the National Academy of Sciences.

As expected, the team observed that restricting food increases longevity in normal healthy mice. Reduced feeding increased lifespan by about 19 percent in normal male mice and by about 28 percent in normal female mice.

However, in sharp contrast to its effects in normal mice, calorie restriction failed to increase lifespan in mutant mice lacking growth hormone receptor. "The present findings show that growth hormone resistant mice fail to respond normally to calorie restriction, a very effective life-extending intervention," Bartke said.

"The key implication of this study is that growth hormone receptor and thus presumably the normal, physiological actions of growth hormone are important in regulation of aging and life span," Bartke said.

The team also found that calorie restriction for 12 months improves insulin sensitivity in normal mice but fails to further enhance the "remarkable insulin sensitivity" in growth hormone knockout mice.

This finding, Bartke said, "supports our hypothesis that increased sensitivity to the actions of insulin is a very important and perhaps the key mechanism of delayed aging and prolonged longevity in growth hormone deficient and growth hormone resistant mice."

SOURCE: PNAS, May 16, 2006.