The biological clock of the worm known as Caenorhabditis elegans ticks fast, but these clever nematodes have a way to put aging on hold. In times of stress, such as food scarcity, they can store up fat and enter a state of suspended animation for 2 months or longer. In tomorrow's issue of Science, a Boston-based research team reports new evidence that nematodes can extend their lives when they detect a shortage of food by slowing their metabolism. The finding suggests a tantalizing connection to aging in mammals--and possibly a way to soften its ravages in humans.
Researchers have known for several years that a gene called daf-2 belongs to a family of genes involved in triggering this suspended animation. Now geneticist Gary Ruvkun at Massachusetts General Hospital and colleagues from Harvard Medical School have cloned and sequenced daf-2, and they report a surprising discovery: The protein it encodes appears to be the worm equivalent of the human insulin receptor. This molecule "listens" for the hormone insulin, which is secreted in response to a rise in blood sugar, and passes its metabolism-enhancing signal to our cells' interiors.
Ruvkun and his colleagues suggest that during times of plenty, the worm maintains high levels of an insulin-like hormone, which binds to the DAF-2 receptor. But when food gets scarce, the hormone-level plummets, DAF-2 binding decreases, and the cell's metabolism shifts into low gear. In other words, the very system the worm uses for monitoring and altering its metabolism is also part of the switch that shifts its metabolism into "suspend" mode, drastically lengthening its life when times are bad.
The finding raises a intriguing possibility: that changes in glucose metabolism could be key to slowing the aging process in higher organisms, including humans. Researchers already know that rats and mice fed very low-calorie diets live longer. If some of the same genetic circuitry triggered in the worms by the DAF-2 signal accounts for this lifespan extension in rats and mice, "that would be a phenomenal discovery," says Don Riddle, a geneticist at the University of Missouri. It might spur the design of drugs that could stretch human lifespans by tricking cells into entering a low-metabolism stage even when they aren't being starved.
Even if the long-lived worms don't show the way to extending human lifespan, they offer researchers a new model system in which to study insulin signaling. And that, Ruvkun and other researchers point out, may improve biologists' chances of designing treatments for diabetes.