Altered Gene Is Creating Fruit-Fly Methuselahs

Mutation of a gene whimsically named “I’m not dead yet” can double the life span of fruit flies, a laboratory discovery that researchers said may lead to drugs to help people live longer and, perhaps, even lose weight.

Researchers at the University of Connecticut Health Center have found that the life span of fruit flies was extended from an average of 37 days to 70 days when a gene was modified on a single chromosome. Some flies in the study lived 110 days.

The same long-life gene exists in humans, said Dr. Stephen L. Helfand, senior author of the study, and “offers a target for future drug therapies aimed at extending life.”

In human terms, a doubled life span would be about 150 years.

Helfand said the gene mutation appears to work by restricting calorie absorption on a cellular level--in effect, putting the cells on a diet. This raises the possibility, he said, of one day developing a pill that would both extend life and control weight.

“From what we know about this gene, that makes perfect sense,” he said.

Helfand said a key finding of the study, which was appearing Friday in the journal Science, is that not only did the fruit flies live longer, but they also seemed to maintain a high quality of life.

“It is not an empty or hollow increase in life span. It prolongs active adult life, and I think, delays the onset of aging,” he said.

Some life-extension studies showed that animals tended to trade vigor and energy for a longer life, he said.

But the mutant flies “do well throughout their longer life,” Helfand said. “By the time that 80% to 90% of normal flies are dead, these mutants are still doing just fine.”

Blanka Rogina, a co-author of the study, said female flies with the mutated genes were able to reproduce throughout life. They had the energy for the fruit fly’s complex courtship ritual and could lay up to 2,000 eggs in their lifetime, compared with about 1,300 eggs normally, she said.

The long-life gene was named for a comical line--”I’m not dead yet”--from a Monty Python movie, Helfand said. The gene’s name was suggested by co-author Robert A. Reenan and has been shortened to “Indy.”

“In academic circles,” explained Helfand, “sophomoric humor, such as in Monty Python, is very common.”

There have been other studies that found long-life genes in fruit flies and nematodes. There also have been experiments in mice that show calorie restriction--a severe diet--can extend life by up to 50%.

But Huber Warner, associate director for research into the biology of aging at the National Institute of Aging, said the Indy gene discovery is more significant because “it may be a different way to get the same effect that caloric restriction achieved in mice and other organisms.”

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He said it may be possible to develop a drug that inhibits metabolism in the same way as the mutated Indy gene. Such a drug would have to be tested extensively in animals to assure that it is safe, Warner said.

“If you wanted to slow metabolism in people, this research suggests that this could be a way to do it,” he said. “It is strictly theoretical right now, but it is a possibility.”

Helfand and his colleagues discovered the live-long gene by chance. He said they were screening a strain of fruit flies in another study and found that flies were living much longer than normal.

They isolated the Indy gene and then tested it in a number of different laboratory fruit fly strains. In all cases, it extended life.

But Helfand said the researchers discovered that if the gene is mutated too much, it actually shortens life.

The normal gene is on two chromosomes of the fruit fly. If one of these genes is altered, thus reducing the strength of the gene, then the flies enjoyed a long life. If both genes were knocked out altogether, said Helfand, the flies actually died sooner, perhaps starving to death.

“If we restrict [the gene] a little bit there is a big advantage,” said Helfand. “But if we make an animal that has only the mutated gene, we find that the animal lives shorter than normal.”

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For more information, go to the National Institute on Aging’s Web site at https://www.nih.gov/nia/ or the journal Science’s site at https://www.eurekalert.org.