Evidence of aging mechanism

SCIENTISTS HAVE provided the first evidence of a hormone-based aging mechanism they suggest may promote long life in species ranging from roundworms to humans. The mechanism begins in the brain with a mutant gene that suppresses the release of hormones that prompt rapid aging.

"This is the first evidence of the way this aging mechanism works," said lead investigator Marc Tatar, of Brown University. "It appears that aging is hormonally regulated, with a brain- based pathway that affects general hormones that come from a pituitary-like system."

The researchers studied a gene with function in the brain and other cells, called an insulin-like receptor (InR). The gene is analogous to those in species from top to bottom of the animal kingdom.

Fly InR responds to a form of insulin. As a result, brain cells tell a thyroid - or pituitary - like system to release a second hormone called juvenile hormone. This compound circulates in the body, unleashing a chain of other events that trigger reproduction and rapid aging.

The researchers bred fruit flies with mutant InR. They believed the mutation suppressed the release of juvenile hormone, arresting the aging process. Indeed, the breeding experiment produced dwarf females with life spans extended by up to 85 percent. Dwarf males also resulted, but they were generally frail and most died by 20 days. Males that survived to 20 days had low subsequent death rates.

To test whether mutant InR had suppressed juvenile hormone, the researchers administered juvenile hormone to treat the long-lived flies. The treatment restored typical life expectancy to the insects. In the brain, an important aging function is taking place, which plays a powerful role in the rest of the body, the scientists said. Their study appears in the journal Science.

"We concluded that juvenile hormone deficiency, which results from mutation in the insulin-like receptor pathway, is sufficient to extend lifespan," said Tatar, assistant professor of ecology and evolutionary biology. "We think that in flies and worms, and probably in humans, insulin-like compounds mediate aging by either retarding growth or by activating specific endocrine tissue to release other hormones."

Scientists may guess which hormones may be involved in human aging, "but we don't know which brain signals or external environmental signals turn on the aging mechanism," he said. "This aging mechanism is something we don't understand at all in humans. But we know something is going on. The neurocircuitry in our brains is similar to that of flies." Aging is much easier to study in flies than in humans, Tatar said. As cold- blooded creatures, flies have a much greater range of adaptability to environmental signals such as light, temperature or food.

Aging is hormonally regulated, with a brain-based pathway that affects general hormones that come from a pituitary-like system.

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