Revisiting Naked Mole Rats and their Lack of Cancer

As you might recall, naked mole rats are interesting to researchers not just because they live nine times longer than similarly sized rodents of other species, but because they don't seem to suffer cancer. At all. There's a primer or two on naked mole rats and cancer back in the Fight Aging! archives:

Naked Mole Rats Do Not Suffer From Cancer

No naked mole rat has been observed to suffer from cancer, a fact that is attracting interest from the cancer research community as this species becomes more widely studied. If the biochemistry that leads to this feat can be understood, it is possible there exists an economical way to port that cancer immunity to humans.

Mechanisms of Naked Mole Rat Cancer Immunity

Like many animals, including humans, the mole rats have a gene called p27 that prevents cellular overcrowding, but the mole rats use another, earlier defense in gene p16. Cancer cells tend to find ways around p27, but mole rats have a double barrier that a cell must overcome before it can grow uncontrollably.

It will be interesting to see whether this line of research pans out into something that looks like a gene therapy for humans. On this topic I see that there's a general interest article on mole rats and their cancer immunity in yesterday's Washington Post:

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.

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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.

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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.

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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.

A similar line of thinking can be applied to the study of whales, species that must also be highly resistant to cancer, given their massive size and life spans that stretch out to more than 200 years in some cases:

Blue whales can weigh over a thousand times more than a human being. That's a lot of extra cells, and as those cells grow and divide, there's a small chance that each one will mutate. A mutation can be harmless, or it can be the first step towards cancer. As the descendants of a precancerous cell continue to divide, they run a risk of taking a further step towards a full-blown tumor. To some extent, cancer is a lottery, and a 100-foot blue whale has a lot more tickets than we do.

There is potentially much that can be learned from the mammalian species - like naked mole rats and the great whales - that share similar cellular biologies but nonetheless manage to be far more resilient or far longer lived than we humans.

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