Why Do Naked Mole Rats Live So Long?

That hairless, wrinkly, fanged rodent in the photo above? It’s a naked mole rat, and deep inside its cells, its molecular machinery might hold the secret to living a very, very long time.

“They are an incredibly striking example of longevity and resistance to cancer,” says Vera Gorbunova, a biologist at the University of Rochester who studies the long-lived rodents, which have been shown to survive for up to 28 years—a lifespan eight times that of similarly-sized mice—and have never once been observed to develop cancer, even in the presence of carcinogens.

In recent years, Gorbunova and her husband Andrei Seluanov have looked closely at the species, which lives in underground colonies in East Africa, hoping to figure out how exactly it manages to survive so long. As revealed in new research her team published today in Proceedings of the National Academy of Sciences, their team thinks they’ve found at least part of the answer: naked mole rats have strange ribosomes.

Every one of our cells (and, for that matter, every living organism’s cells) converts the genetic instructions present in our DNA into proteins—which control a cell’s overall operation—through a process called translation. Tiny microscopic structures called ribosomes handle this translation, reading genetic instructions that specify a particular recipe and churning out the protein accordingly.

The ribosomes in almost every multicellular organism on the planet is made up of two large pieces of RNA, a genetic substance similar to DNA. But last year, one of the Rochester lab’s students was isolating RNA from cells taken from the naked mole rats when he noticed something unusual. When he separated the RNA pieces, instead of seeing two distinct pieces of ribosomal RNA, he saw three.

“At first, we thought we were doing something wrong and it’d gotten damaged,” Gorbunova says. “Because for all mammals, you’d see two, but we kept seeing three.”

After a variety of testing confirmed that it wasn’t an experimental error, they decided to look more closely at the potential effects of this unusual structure. Other research had suggested that artificially interrupting the translation process to make ribosomes less accurate could produce poorly-built proteins that accumulate and lead to cell death, which raised the possibility that the mole rats’ unusual ribosomes did the opposite—producing fewer transcription errors and extending lifespan. To test the idea, Gorbunova developed a means of seeing just how accurate the mole rats’ ribosomes were at converting genetic instructions into proteins.

It turned out that, compared to mouse ribosomes, these three-part structures made between four and forty times fewer errors during the translation process. At this point, it’s unclear how exactly that might lead to longer lifespans, but the researchers believe it plays a key role.

Even so, the rodents appear to benefit from other, unrelated mechanisms that allow them to live uncommonly long lives. In June, Gorbunova and Seluanov announced the discovery that the rodents also produce a novel cellular compound that appears to prevent them from getting cancer.

Both of these mechanisms prompt an obvious question: Why are naked mole rats blessed with these anomalous, life-extending characteristics? “It’s not random,” Gorbunova says. “It has to do with the ecology of the species.”

Because the rodents live underground, in ultra-social colonies, she explains, they’re much less prone to random deaths caused by accidents or predation. The fact that the risk of dying randomly is so much lower means that, from an evolutionary standpoint, it makes more sense to invest in cellular mechanisms that might allow the creatures to live longer. Even if a mouse had three-part ultra-accurate ribosomes and cancer-fighting substances, in other words, it’d probably be eaten within a year by a predator anyway, so it never had the chance to evolve mechanisms that would allow it to live to 28.

But the naked mole rats did. Gorbunova and Seluanov want to proceed by seeing whether either of their special mechanisms—longevity or cancer resistance—could be introduced into mouse cells, and whether they might lead to corresponding extensions in lifespan. If they’re successful, they hope that, someday, we might even be able to extend our own lifespans by copying the naked mole rats’ success.

Joseph Stromberg | | READ MORE

Joseph Stromberg was previously a digital reporter for Smithsonian.