Naked Mole Rats and Cancer Research

voraciousreader

 From The Washington Post:

Researchers try to understand naked mole rats' resistance to
cancer

By Ivan Amato
Monday, March 7, 2011; 6:30 PM

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

chrissyb

Always knew they were interesting all be it ugly little critters.  Thanks for the article on a very interesting line of research.

JohnSmith

So much for the "Naked Mole Rat" never getting cancer theory...

Cancer Detected in Naked Mole Rats
Two captive males of the cancer-resistant species have shown signs of malignant tumors.

February 8, 2016

The naked mole rat, Heterocephalus glaber, is a wrinkly rodent renowned for its ability to stave off cancer. Although the animals can live for 30 years, there have been no documented cases of malignancies in naked mole rats - until, that is, last week (February 4, 2016).

Researchers from the University of Washington and their colleagues reported in Veterinary Pathology that two males, aged 20 and 22 years, had cancerous tumors. "Although these case reports do not alter the longstanding observation of cancer resistance, they do raise questions about the scope of cancer resistance and the interpretation of biomedical studies in this model," the authors wrote in their study.

From the older mole rat, who is still alive at the Brookfield Zoo in Illinois, the team examined a lump from beneath the skin and determined it to be an adenocarcinoma, likely originating from the mammary or salivary gland. The researchers diagnosed the deceased, younger mole rat—who resided at the National Zoo in Washington, DC - with gastric neuroendocrine carcinoma after removing a mass from his stomach. He had been euthanized because of skin problems and weight loss.

"For the adenocarcinoma (Case No. 1), questions still remain regarding its histogenesis as well as its eventual impact on the health and life span of the affected NMR [naked mole rat]. The gastric neuroendocrine carcinoma (Case No. 2) likely contributed to the [naked mole rat's] inability to maintain body weight, which was a primary reason for euthanasia," the authors wrote.