Originally created 04/07/01

Hormones could play part in extending life span

Researchers are finding the first evidence of hormonal-based aging mechanisms that may promote long life in species ranging from fruit flies and roundworms to humans.

Three studies reported Friday in the journal Science indicate that the insulin-signaling pathway acts to regulate aging in a number of organisms.

And because insulin signaling is influenced by how much an animal eats, the scientists also suggest that restricting calories might extend life span in humans and other animals, just as it's already been shown to do in rodents.

"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," said Marc Tatar, lead investigator of one research team at Brown University.

Tatar, an assistant professor of ecology and evolutionary biology, and colleagues generated a line of fruit flies with a mutation in the insulin-receptor gene. The mutant flies had impaired neuroendocrine function that suppressed release of a juvenile hormone, arresting the aging process.

In fact, the breeding experiment produced dwarf females with life spans up to 85 percent longer than normal insects of the same species. Dwarf males also were born, but they were generally frail and most died within 20 days. Males that lived past the first 20 days, however, had lower-than-normal death rates. The flies normally live about 60 days.

A second group, led by David Clancy of the University College London, reported that another gene mutation that changes the code for another insulin-signaling molecule, extended the life span of fruit flies by up to 48 percent.

And in a third study by Italian researchers, two mutations in a similar gene in yeast was found to increase resistance to free radicals that foster aging and extend the life span by up to threefold.

Scientists have earlier identified similar life-extending genes in nematodes, a type of worm, which are also involved in the insulin-insulin growth factor pathway. Thomas Johnson, a biologist at the University of Colorado, and colleagues have cataloged more than 60 genes that can significantly lengthen or shorten nematode life spans.

Tatar said "it appears that aging is hormonally regulated, with a brain-based pathway that affects general hormones that come from a pituitary-like system."

But it's still guesswork about which hormones and genes are involved in human aging. "We don't know which brain signals or external environmental signals turn on the aging mechanism," Tatar said. "But we know something is going on. The neurocircuitry in our brains is similar to that of flies."

Aging is also much easier to study in flies than humans, since they're cold-blooded and have a much greater range of adaptability to signals such as light, temperature or food. All of these may trigger reproduction and rapid aging.

"Our brains function in a narrow range of physiological states and perhaps cannot adapt to signals that in cold-blooded organisms may prompt long life," Tatar said. "Humans don't adapt to environments. We adapt environments to us."

Even though the signaling is much more complex in humans, and likely involves hundreds of hormones, scientists say the evidence makes further studies in higher species, like mice and rats, worthwhile.

Tatar said his team is still working with flies to determine how the hormone regulates aging beyond just metabolism, such as whether it increases the insects' resistance to stress or ability to fight disease.

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