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How naked mole rats stay cancer-free

Image via University of Rochester photo/J. Adam Fenster.

If you like cute, naked mole rats might not be your favorite rodent. They have large buck teeth and wrinkled, hairless bodies. But researchers find them intriguing. That’s because naked mole rats have the longest lifespan of any rodent (average is 30 years), they’re resistant to a variety of age-related diseases – such as cancer – and tend to remain fit and active until very advanced ages. What’s their secret?

A new paper published December 28, 2017, in the journal PNAS suggests part of the answer might lie in an anticancer mechanism called cellular senescence, which, the researchers suggest, operates in a special way in mole rats.

Image via redbrick.

Cellular senescence is an evolutionary adaptation that prevents damaged cells from dividing out of control and developing into full-blown cancer. However, senescence has a negative side too: by stopping cell division in order to prevent potential tumors, it also accelerates aging.

Previous studies have indicated that when cells that had undergone senescence were removed from mice, the mice were less frail in advanced age as compared to mice that aged naturally with senescent cells intact.

But is eliminating senescence actually the key to preventing or reversing age-related diseases, namely cancer? Vera Gorbunov of the University of Rochester is a study author. She said in a statement:

In humans, as in mice, aging and cancer have competing interests. In order to prevent cancer, you need to stop cells from dividing. However, to prevent aging, you want to keep cells dividing in order to replenish tissues.

For the study, the researchers compared the senescence response of naked mole rats to that of mice, which live a tenth as long — only about two to three years. Researcher Andrei Seluanov is a University of Rochester biology professor. Seluanov said:

We wanted to look at these animals that pretty much don’t age and see if they also had senescent cells or if they evolved to get rid of cell senescence.

Their unexpected discovery? Naked mole rats do experience cellular senescence, yet they continue to live long, healthy lives; eliminating the senescence mechanism is not the key to their long life span. Gorbunova said:

It was surprising to us that despite its remarkable longevity the naked mole rat has cells that undergo senescence like mouse cells.

The researchers found that although naked mole rats exhibited cellular senescence similar to mice, their senescent cells also displayed unique features that may contribute to their cancer resistance and longevity.

The cellular senescence mechanism permanently arrests a cell to prevent it from dividing, but the cell still continues to metabolize. The researchers found that naked mole rats are able to more strongly inhibit the metabolic process of the senescent cells, resulting in higher resistance to the damaging effects of senescence. Gorbunova said:

In naked mole rats, senescent cells are better behaved. When you compare the signals from the mouse versus from the naked mole rat, all the genes in the mouse are a mess. In the naked mole rat, everything is more organized. The naked mole rat didn’t get rid of the senescence, but maybe it made it a bit more structured.

Although evolution of a long life span does not eliminate senescence, the more structured response to senescence may have an evolutionary basis, said Yang Zhao, lead author of the study.

We believe there was some strategy during the evolution of naked mole rats that allowed them to have more systematic changes in their genes and have more orchestrated pathways being regulated. We believe this is beneficial for longevity and cancer resistance.

Bottom line: New research into the puzzle of how naked mole rats stay so cancer-free.

Read more from the University of Rochester

February 28, 2018

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