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.
Female mice lacking S6K1 lived an average of 950 days, over 160 days (or 20 percent) longer than the control group. For humans, that would be like adding 16 additional years of life.
Male mice, however, received little benefit from the single gene removal.
Female mice not only lived longer, but also were healthier and leaner. They had stronger bones, were more curious in their environment, had better regulated immune systems, were protected from Type II diabetes, and even saw improvements with other age-related ailments.
"We added years of life, but also life to those years," said Withers.
Other scientists, including Matt Kaeberlein, a scientist at the University of Washington who wrote an accompanying perspective for Science, are excited about the new study.
"I think there are lots of reasons to be optimistic that targeting this pathway could have therapeutic uses for age-related diseases," said Kaeberlein, adding that targeting the specific S6K1 pathway might be a better option than using rapamycin.
Cynthia Kenyon at the University of California, San Francisco, who studies longevity in worms, says the research could eventually be used to extend the lives of humans.
"This absolutely could have clinical uses," for human patients, said Kenyon. "This is a great result but not really surprising because knocking this gene out in worms and yeast extended their life spans."
However, the study doesn't imply that healthy folks should start taking metformin.
"I don't think (taking metformin) is a substitute for a healthy lifestyle," said Withers, adding that more studies are necessary before he would feel comfortable prescribing metformin for healthy, non-diabetics.
If millions of people have been taking metformin and rapamycin for decades, why hasn't anyone noticed, especially long-lived and healthy diabetics and organ transplant patients?
The simple answer, according to scientists, is that no one was looking.
Diabetes and organ transplants are serious enough that scientists didn't expect these patients would be able to live measurably longer than non-diabetic or organ transplant patients. As far at Kaeberlein and Withers know, no scientist has published a study looking at the life span of diabetic or organ transplant patients.
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