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January 22, 2001

Gene That Doubles Fruit Fly Life Span
May Extend Human Life, Say Scientists

Scientists at the UConn Health Center have discovered a gene that doubles the average life span of fruit flies. The gene is also found in humans. This discovery opens the way for new therapies that could extend human life.

An article in Science is a notable achievement and the attendant media attention can be worldwide. Commercial media outlets carrying the Indy gene story included The New York Times, the Associated Press, Reuters, CNN, ABC World News Tonight, Fox News Network and National Public Radio.

Internationally, reporters from media outlets in Sweden, Germany, the United Kingdom, Argentina, Austria, Germany and Canada called. Individual outlets publishing the story included newspapers in the U.S. from the Los Angeles Times to the Newburyport, Mass., Daily News and from The Tampa Tribune to the Idaho State Journal in Pocatello.

Electronic outlets in the U.S. ranged from WBZ Radio in Boston to KPRC Channel 2 in Houston, and everywhere in between. At one point in the media flurry, principal investigator Steven Helfand, on sabbatical in Britain, found himself walking down a London street, talking to The New York Times on a cell phone. Another time he was on a train heading for Wales and was talking on a cell phone to the British Broadcasting Corp.

Robert Reenan, one of the investigators, says he found the experience enjoyable: "It was fun," he says. "It's definitely nice to have people in general interested in the work we do."

The research, published in the Dec. 15 issue of Science, identifies and describes a gene that has been manipulated in the laboratory so that its normal activity decreases, thereby permitting the fruit fly to live longer.

This gene - named "Indy" in homage to the tagline "I'm Not Dead Yet" in the 1975 comedy, "Monty Python & The Holy Grail" - has been subjected to multiple, independent mutations that all result in extended life span. This is equivalent to an average human life span of 150 years. Crucially, quality of life is not sacrificed in these long-lived fruit flies. They also remain physically and sexually active longer.

In both humans and fruit flies, the Indy gene is found where the body stores energy and uses it. Indy absorbs essential nutrients through the gut, concentrates them in the liver, and reabsorbs them via the kidney.

The researchers suspect that humans have more of this type of gene than do fruit flies, given that people are more complex than insects. Whereas manipulation of a single gene affects the fruit fly's life span, in humans it may be necessary to alter multiple related genes.

Stephen Helfand, principal investigator and an associate professor of genetics and developmental biology, suggests that "these mutations in the Indy gene may cause a form of caloric restriction. Calories either don't get absorbed or are wasted." Caloric restriction is the only way known to extend the life span of mammals.

These Indy mutations may be creating a genetic caloric restriction. "It would be as if the Indy animal can eat as much as it wants without becoming obese, live twice as long as average, and still retain normal function and activity," speculates Helfand.

Co-investigator Blanka Rogina, an assistant professor of genetics and developmental biology, says, "Our next goal is to show that the effect on extending life span is indeed due to caloric restriction. We are eager to follow our study with experiments to understand how life span extension is achieved."

Helfand believes "The Indy gene should provide direct information on the role of energy balance and aging. It offers a target for future drug therapies aimed at extending human life. In fruit flies, the Indy gene mutation doesn't make infancy last longer, but it does prolong active adulthood and delays the onset of aging."

Robert Reenan, a co-investigator and an assistant professor of genetics and developmental biology, expects that this work may also help humans achieve and maintain their ideal body weight.

Reenan adds that if Indy's major role in humans proves to be that of absorbing nutrients from the intestine, then drugs can be designed which act upon the gut without being transmitted throughout the body. Such medications would have low toxicity and be non-invasive. They might have fewer side effects and attack only where needed.

Staff reports

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