Lord of the (Ancient) Files
POSTED 15 DEC 2000

Related Why Files:
1. Fighting fat.
2. Fast fat fixes
3. Down at the ant farm


I'm not dead yet!



The green curve shows survival of Indy mutant flies. The blue curve shows survival of control flies, and of flies where the Indy mutation was removed.
Data from "Extended Life-Span..." (see below).























Damaging one gene almost doubled the fly's lifespan.











Micrograph of a fruit fly
© Dennis Kunkel

Micrograph of a fruit fly's head
Micrograph of a fruit fly's head
© Dennis Kunkel
To live longer, starve yourself a bit. That's the paradoxical implication of studies from fruit flies, rodents and mammals. The only proven way to extend the life span of a mammal is to cut calories about 30 percent.

It works, but few people can sustain such a Spartan diet.

Caloric restriction may work by reducing concentrations of free radicals -- highly reactive molecules that degrade essential biological compounds.

Now comes a hint about the mechanism from "fly guys" -- the subculture in biology that studies fruit flies. Fruit flies are the Vise-Grips of genetics and developmental biology -- a cheap, versatile, and practical research tool.

And the flies, it turns out, have a gene dubbed "Indy" (named, not for the race, but for "I'm not dead yet"). If you throttle back the Indy gene, the flies live twice as long.

Now we could metamorphose the fiction of Franz Kafka and point out that the only thing worse than being a fly is being a fly and living twice as long. graph of fly survivorshipBut that's narrow-minded.

And besides, humans have a gene similar to Indy, and the new discovery might eventually help extend the human life span.

So put down that flyswatter and read what all the buzz is about.


Winged senior citizens
The Indy gene was found during a study by Stephen Helfand and colleagues at the Connecticut Health Center on the biological markers of aging. New finding about old genes!These are the biochemical equivalents of those "horrid age spots" that appear as fruit flies become eligible for the AARP invertebrate division. In other words, markers are measurable changes in body chemistry that accompany aging.

Specifically, Helfand's lab was studying changes in the activity, or expression, of various genes during aging. They used "transposons," movable hunks of DNA that, like spies with radios, can be inserted into a gene to report whether the gene is working or just lurking.

For obvious reasons, the little spies are called "reporter genes," and Helfand's group noticed that certain reporter genes caused two separate lines of fruit flies to live about 70 days -- almost twice as long as 37 days, the normal average.

Normal people might have stopped to wonder why even a creature as weird as a fruit fly would consider bugdom that enjoyable, but the Connecticut researchers are "fly guys" ...

While exploring the increased survival, the researchers found that both reporter genes reduced the output of a single gene involved in nutrient metabolism. In the simplified language we Why Filers crave, the gene helps recruit sugars and other molecules to make adenosine triphosphate (ATP).

ATP is everywhere. Robert Reenan, a University of Connecticut developmental biologist who helped write the new study, calls it the "hard currency of biological energy."

And that, Reenan says, returns us to the calorie-counting technique for life span extension. "Since Indy's normal function is probably to cause the uptake of nutrients from the gut, our working hypothesis is that it mimics, in a genetic way, a specific kind of caloric restriction."

Indeed, the gene could help produce the Holy Grail -- a way to get the benefits of caloric restriction without the agony of extreme-sport dieting.

Remember, the flies ate whatever they wanted, even imported mangoes (just kidding).

Fertility symbol
A satisfying diet is one key to a healthy life. A second is a vibrant family life. And while it's known that virgin female flies live longer than usual (who said parenthood would be free?), the elderly mutant females in the study actually had twice as many young as usual.

picture of a whole, small flyThat discounts a second possible explanation for their longevity, Reenan says: The mutated flies showed no reduction in reproduction.

And because fertility requires complex behavior, he adds, it indicates that the flies have a good quality of life. Seriously. "Fertility is the result of a series of long and complex events," Reenan explains. "The male produces mating cues, the female has to respond with her own mating cues, there's locomotor activity in copulation, you have to be able to find a place to lay eggs, then lay the eggs."

The data on reproduction, Reenan says, "is some of the sexiest data in the paper."

On a more practical level, knowledge of the Indy gene, and the protein it makes, could (possibly, perhaps, maybe, one day, eventually) become the basis for a drug that mimics the mutation and extends human life span.

If only we should live so long.

-- David Tenenbaum



Extended Life-Span Conferred by Cotransporter Gene Mutations in Drosophila, Blanka Rogina et al, Science, 15 Dec. 2000, pp. 2137-40.

Franz Kafka, Collected Stories; edited and introduced by Gabriel Josipovici, Knopf , 1993. Related Why Files  




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