With its wrinkled skin and bucked teeth, the naked mole rat isn't going to win any beauty contests. But the burrowing, desert rodent is exceptional in another way: It doesn't get cancer. The naked mole rat's cells hate to be crowded, it turns out, so they stop growing before they can form tumors. The details could someday lead to a new strategy for treating cancer in people.
In search of clues to aging, cell biologists Vera Gorbunova, Andrei Seluanov, and colleagues at the University of Rochester have been comparing rodents that vary in size and life span, from mice to beavers. The naked mole rat stands out because it's small yet can live more than 28 years--seven times as long as a house mouse. Resistance to cancer could be a major factor; whereas most laboratory mice and rats die from the disease, it has never been observed in naked mole rats.
Gorbunova's team looked at the mole rat's cells for an answer. Normal human and mouse cells will grow and divide in a petri dish until they mash tightly against one another in a single, dense layer--a mechanism known as "contact inhibition." Naked mole rat cells are even more sensitive to their neighbors, the researchers found. The cells stop growing as soon as they touch. The strategy likely helps keep the rodents cancer-free, as contact inhibition fails in cancerous cells, causing them to pile up.
The reason, the researchers discovered, is that naked mole rat cells rely on two proteins--named p27Kip1 and p16Ink4a--to stop cell growth when they touch, whereas human and mouse cells rely mainly on p27Kip1. "They use an additional checkpoint," says Gorbunova, whose study appears online today in the Proceedings of the National Academy of Sciences (PNAS). When the team mutated the naked mole rat cells so that they grew much closer together than they had before, levels of p16Ink4a dropped.
The naked mole rat's kind of cancer prevention may prove relevant to humans because the same genes are involved, says Brown University cancer biologist John Sedivy. The rat's defenses "evolved separately but use the same nuts and bolts," he says. Sedivy writes in an accompanying commentary in PNAS that it may be possible to "tweak the entire network [of tumor-suppressing pathways] to develop new prevention strategies."
The next step, Gorbunova says, is to find other proteins and molecules that make up this new contact inhibition pathway. One obstacle is that little is known about the naked mole rat's genes. The critter has been proposed for genome sequencing but so far has been turned down. "I hope Vera's study will put the naked mole rate higher up in the queue," says George Martin, a researcher who studies aging and a professor emeritus at the University of Washington.