Mice Get Benefits of Dieting Without the Diet

Oct. 1, 2009 -- Diet and exercise may not be the only route for a longer, healthier life, according to a new study. By deleting a single gene, scientists have extended the life span -- and life quality -- of female mice.

The most popular diabetes drug in the United States, metformin, targets the same proteins produced by the deleted gene, raising the possibility that millions of people might have been taking a life-extending drug for the last 50 years.

"There was a broad spectrum of improvement beyond life span," said Dominic Withers, a scientist at University College London and co-author of a paper that appears in today's issue of Science.

Female mice without the gene were "leaner, had stronger bones, were protected from Type II diabetes, had better balance and coordination, were more inquisitive in their environment and also had more youthful immune systems." Interestingly, male mice didn't reap the same benefits.

Extending the human life span has been a hot area of research for years. Severely restricting the diets of yeast, bacteria, mice and primates have granted these animals unnaturally long lives.

For humans, however, maintaining a diet of near starvation would be difficult at best. For this reason, scientists have sought drugs that mimic the effects of caloric restriction while allowing a person to eat normally.

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The drug with the most publicity is resveratrol, a compound found in red wine that extends the life of fruit flies and worms and protects mice against diabetes. In July, a Nature article showed that rapamycin, a drug used to suppress the immune system of organ transplant patients, extended the lives of mice by as much as 38 percent.

Rapamycin targets proteins that affect the immune system, nutrient regulation, metabolism and stress. One such protein, called S6 kinase 1 (S6K1), helps to regulate energy metabolism.

Metformin, the most popular diabetes drug in the United States, is thought to lower S6K1 levels. By targeting only S6K1 scientists hope to create the life-extending effects without the immune suppression effects of rapamycin.

Withers and his colleagues didn't add metformin to the diet of mice, but instead used genetic engineering to remove the gene that produces S6K1. After 600 days, the scientists compared a couple hundred S6K1-removed mice with a couple hundred control mice.