Researchers try to understand naked mole rats' resistance to

cancer

With their pinkish, translucent and wrinkly skin, double-saber buck teeth and black-bead eyes,
naked mole rats look like characters in a nightmare from hell. In fact, they do live underground in
pitch-dark burrows where their air, from a human point of view, can contain chokingly little oxygen,
toxic carbon dioxide levels and a perpetual stench of ammonia. What's more, even though they are
mammals, these sausage-size rodents live more like ants and bees, with a queen, a few mating males
and lots of workers.
But one other thing: They apparently never ever get cancer, which has made naked mole rats
particularly beautiful to scientists.
In the past few years, researchers have been teasing out the biological bases for this cancer
resistance, which they say may help explain how naked mole rats manage to live almost 10 times
longer than their house mouse and street rat cousins. When Old Man, the oldest known naked mole
rat on the planet, died at the University of Texas Health Science Center in San Antonio in November,
he was 32 years old.
"These animals beat the odds and defy the aging process," says Rochelle Buffenstein, a physiologist
at the center who had her scientific eye on Old Man since 1980, when she and colleagues captured
him in a Kenyan sweet potato field. Now she maintains colonies with about 2,000 naked mole rats in
her lab.
"A key finding of our work is that every physiological and biochemical system within the naked mole
rat shows extended maintenance, leading to good health." Only in Old Man's final few years did he
begin to appear sort of old. For most of his senior citizenhood, Buffenstein and her colleagues
observed, his bones, muscles, heart and libido seemed like those of a teenager.
Getting old without the usual diseases and diminishments of the aging process has always been an
intriguing idea. Vera Gorbunova, a biologist and cancer researcher at the University of Rochester in
New York, is among those scientists trying to find out how naked mole rats do it. Most tantalizing to
Gorbunova is that naked mole rats never get cancer even though 70 percent or more of mice that
live even a few years die of cancer.
For many of the experiments her team wanted to do, they needed to grow naked mole rat cells in
laboratory dishes, but this proved to be difficult. Whenever the cells touched one another, they
stopped replicating. This was frustrating, but it also presented Gorbunova with a clue. She knew that
normal mouse and human cells exhibit a less pronounced type of "contact inhibition" and that cancer
cells grow into masses because they lack this inhibition.
"In naked mole rat cells," Gorbunova surmised, "we are seeing super contact inhibition." She
wondered if there might be a linkage with the mole rats' immunity to cancer.
When the researchers dug deeper, they made a remarkable discovery that went all of the way down
to the animals' genes and the biochemistry of their cells. "Naked mole rat cells possess two levels of
contact inhibition, in contrast to the single level found in humans and mice," she and her colleagues

wrote in late 2009 in the journal Proceedings of the National Academy of Sciences.
As Gorbunova sees it, living a long time and disease-thwarting mechanisms such as super contact
inhibition go hand in hand. Mice are valuable animal models for studying cancer precisely because
they get the disease so easily, she notes, and naked mole rats should become just as important for
cancer research precisely because they never get the disease.
Her team is looking into potential therapeutic openings by which they might instigate super contact
inhibition in other settings - say, in precancerous tissue of humans to stop the disease process in its
tracks.
There's more to naked mole rats, though, than longevity and cancer resistance.
"Their pain biology is unique among animals," notes neuroscientist Thomas J. Park of the University
of Illinois at Chicago. He and his colleauges have observed that the skin cells of naked mole rats lack
certain pain-related signaling molecules. The animals appear undisturbed by acid and a hot-pepper
irritant that bother other animals, including people. From this, the scientists hope to develop new
means of pain management for humans.
Then there's the animals' ability to live without much oxygen. On that front, molecular evolutionary
biologist Aaron Avivi of the University of Haifa in Israel and his colleagues have focused on the
Spalax genus of mole rat, which he describes as a "hairy sausage whose ends are hard to tell apart."

Unlike the naked mole rat, Spalax

individuals live solitary lives, are
aggressive and cannot be bred in
captivity. "Living underground has led to
a lot of adaptations," Avivi says,
including the ability to thrive in
atmospheres that would quickly kill a
human.
Especially during the winter in their
northern Israeli habitats, there are days
of intense rain that flood the mole rats'
sealed tunnel systems. Oxygen concentrations dive to one-seventh that of normal above-ground
levels, while carbon dioxide levels spike by a factor of 200, conditions that would permanently off
most other air-breathing animals. Avivi says that developing a full understanding how the animals
can shrug off such conditions holds great biomedical promise because of "its connection to ailments
that practically kill the Western world," among them cancer, vascular and heart disease, heart
attacks and strokes.
If for the past 24 million years you and your ancestors have lived in dark, dank subterranean niches,
as have naked mole rats, you will have evolved plenty of adaptations in response to your habitat. And
understanding those adaptations might well help us above-ground naked.
Amato is a writer and editor based in Silver Spring.
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