We can learn a lot from the naked mole rat. By defying the biological laws of aging, these hardy little rodents can live into their 30s, they're all but immune to cancer, and they can go without oxygen for extended periods by mimicking plants. Researchers at the University of Rochester had a theory on how they manage to live such long lives: perhaps their cells didn't undergo the process of senescence. But when they looked at the cells of naked mole rats, they found the story is much stranger.

Cancer is essentially just a collection of unruly cells that keep dividing out of control. To keep them in check, humans and other organisms have evolved a defense mechanism known as cellular senescence, which stops damaged cells from dividing any further. But the flipside is that as these inactive, senescent cells build up in the body, they contribute to the physical deterioration we see as products of aging.

"In humans, as in mice, aging and cancer have competing interests," says Vera Gorbunova, co-author of the new study. "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."

Removing senescent cells has emerged as a promising anti-aging therapy in recent years. Mouse studies have found that doing so can extend the animals' lifespans by up to 35 percent, and keep them in better health for longer. That has inspired a new class of drug, called senolytics, designed to bring those benefits to humans.

The Rochester researchers wanted to compare the senescence response of naked mole rats to that of mice. Given the unusual biology of the naked mole rats, the team suspected the rodents were doing something strange with this fundamental cellular process.

"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," says Andrei Seluanov, co-author of the study.

And sure enough, there was some weirdness involved. It turns out that naked mole rats don't owe their longer lifespan to ditching senescence altogether, but they do have some unique control over the process. Normally, senescent cells can still metabolize, which can lead to some of the damaging affects of aging. But naked mole rats are able to inhibit that metabolism, contributing to their longevity and resistance to aging.

"In naked mole rats, senescent cells are better behaved," says Gorbunova. "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."

The research was published in the journal PNAS.

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