Fruit flies made extra antioxidants -- and lived much longer.

Does this guy look radical? Professor William Orr makes superannuated fruit flies...Images courtesy Southern Methodist University

In a two-step reaction, SOD converts O 2º to H 20 2. Then catalase converts H 2O2 to molecular oxygen and water.

New progress against aging

Long live the fruit flies
By manipulating genes, a group of Southern Methodist University researchers tempus fugithave created a race of oldster fruit flies. These latter-day Methuselahs live an average of 75 days, compared to 40 to 50 days for common fruit flies.

The achievement was not intended to immortalize the annoying haze of bugs that seem to (but don't) form by themselves around every battered banana and squished squash. Nor was it an effort to threaten the business interests of fruit-fly funeral directors. In reality, the goal was to nail down the role of antioxidants and free radicals in the aging process. willian orr

Pop quiz: Free radicals. Are they former revolutionaries, or some kind of weird fifth-column saboteurs inside your cells?

Let's use the second definition. Free radicals -- nowadays called "reactive oxygen species" are busybody chemicals, usually containing oxygen, that rapidly react with other chemicals. Free radicals damage proteins, DNA and lipids, generally causing mayhem inside cells.

The presence of too many free radicals creates a condition called "oxidative stress" in a cell. In response, cells -- no dummies -- manufacture antioxidants. These enzymes convert free radicals into harmless chemicals like oxygen and water.

According to William Orr, a biology professor at Southern Methodist University who created the superannuated fruit flies along with colleague Rajindar Sohal, the prime antioxidant enzymes are superoxide dismutase (SOD) and catalase.

Does aging = burning up?
Orr says the oxidative stress hypothesis offers a general explanation of aging. The hypothesis predicts that the level of oxidative stress should increase with age (as it does in fruit flies and mammals). It also predicts that increased levels of antioxidants should reduce oxidative stress and extend the life span.

To test the second prediction, Orr and associates manipulated the genes of some fruit flies to make transgenic animals that produced more SOD or more catalase. These animals did not live longer than the average fruit fly. But when transgenic lines were created that simultaneously over-expressed both enzymes, the average life span jumped from 45 to 75 days.

The flies' oxygen consumption increased and they were more active than the controls. This suggests that flies did not extend their life span by reducing their metabolic rate or entering a state of semi-hibernation.

Because the life span was extended only when two enzymes were present, Orr concluded that they collaborate to disarm free radicals by converting them to oxygen and water. SOD, he says, converts the O2º to H202.

Catalase, in turn, converts H2O2 to molecular oxygen (O2) and water. Unfortunately, too much of a good thing is not good at all, Orr says. Increasing SOD without simultaneously increasing catalase would increase the levels of H2O2. And H2O2 is a reactive oxygen species that can cause damage. (However, it's not a free radical, since it does not have an unpaired electron.)

The results were widely heralded among aging researchers, and were "the first direct evidence for the oxidative stress hypothesis," Orr says. The next step, he says, will be to see if the same genetic alteration affects the life span of mammals. "Such studies are under way with mice," he adds, "but it will take time to see results because mice live longer than fruit flies."

But what does oxidative stress have to do with caloric restriction?

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