Mole Rats Senescent Cells Strongly Inhibit their Metabolic Process, Resulting in Higher Resistance to Damage that can Cause Cancer

Another clue to how naked mole rats live long, cancer-free lives - Futurity

Researchers have found that while naked mole rats do have a specific mechanism to keep older cells from dividing, the mechanism operates differently in the small rodents, which may be another clue to the mystery of why they live so long and stay so healthy.

 From article (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 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.

So, researchers believed senescence held the key to the proverbial fountain of youth; removing senescent cells rejuvenated mice, so perhaps it could work with human beings. Companies began investigating drugs—known as senolytic agents—that would kill senescent cells and translate the anti-aging effects to humans.

But is eliminating senescence actually the key to preventing or reversing age-related diseases, namely cancer?

“In humans, as in mice, aging and cancer have competing interests,” says biology professor Vera Gorbunova. “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.”

In the new 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.

“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,” Seluanov says.

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.

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 discovered 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.

“In naked mole rats, senescent cells are better behaved,” Gorbunova says. “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.”)

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