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Naked mole rats show us how to build a better protein

Naked mole rats’ long lifespan and resistance to disease may give us clues to living longer healthier lives. Photo by Brandon Vick/University of Rochester

A naked mole rat will never win a beauty contest. But the nearly hairless rodents, with their sparse whiskers, big buck teeth, wrinkly skin and scraggly tails, may hold clues to longer, healthier lives.

The cells of naked mole rats seem to build better proteins, which may explain their immunity to diseases like Alzheimer’s and Parkinson’s disease, according to a study published this week in the Proceedings of the National Academy of Sciences.

Naked mole rats are unusual creatures. They are cold-blooded, and live in strict hierarchical colonies like ants, with one breeding “queen” and lower ranks of soldiers and worker mole rats. They separate their lower teeth like chopsticks to dig their tunnels and underground nests — and they do so without swallowing dirt.

It’s been known that these rodents can live up to 30 years – that’s eight to 10 times that of mice and other rats. Their bald, wrinkly skin is impervious to pain from acid burns – they lack the neurotransmitters that would cause a painful reaction, studies have shown. And most notably, they are also resistant to cancer. This new study takes the mystery of their unusual longevity a step farther.

While researching the rats, Vera Gorbunova and her husband Andrei Seluanov at the University of Rochester came across something unusual in the naked mole rat ribosomal RNA. While extracting the RNA, they noticed that one of the ribosomal RNA molecules — the 28s — split into two unequal parts. They had never seen this sort of split before.

“I said, ‘there’s got to be something going on here,'” Gorbunova said.

Ribosomes take instructions from DNA to build the proteins our body needs to function, churning them out like machine, in a process called protein translation.

But it isn’t a perfect machine, and it often it makes mistakes, leaving misshapen “junk” proteins. When you’re young, the body recycles the junk, but over time, these misshapen proteins can stick together. This is called protein aggregation and can lead to Alzheimer’s and Parkinson’s disease.

Naked mole rats are resistant to aging related diseases like Alzheimer’s, Parkinson’s and even cancer. Photo by Brandon Vick/University of Rochester

Gorbunova and Seluanov’s study found that the naked mole rats’ ribosome made fewer mistakes during protein translation than that of mice. To study the process, Gorbunova and Seluanov constructed a “tester gene” that codes for the glowing protein found in fireflies. They mutated the gene, so that only an additional mistake made by the ribosome would activate the glowing protein; the more mistakes, the brighter glow. This allowed the scientists to watch accuracy of the protein translation process.

The naked mole rats’ ribosome, they found, made four to 10 times fewer mistakes than the mice.

The findings, while intriguing, don’t explain definitively why these animals live so long, Gorbunova said. But this may provide an important part of the picture.

Brian Kennedy, president of the Buck Institute, a center that researches aging, called it a good starting point. Altering the protein translation process has already been proven to extend the life spans of yeast and other invertebrates, he said. But he added that there are so many factors that affect aging, it’s hard to determine at this point how protein translation fits into the bigger picture.

“Humans have been trying to understand and delay aging for hundreds of years,” Kennedy said. “If we put our efforts in that direction, it’s feasible that we’ll find ways to keep people healthier longer by delaying aging in the not too distant future.”

Studying naked mole rats’ longevity could also inform research for drugs or other therapies that could slow down the aging process, said Rich Miller, professor of pathology at the University of Michigan.

“Overall if you had to pick 15 pathways that are really important in aging, translational control would be on that shortlist,” he said.

Ultimately, Gorbunova hopes studying naked mole rats will lead to increased human life spans, and more importantly, improving our quality of life as we age — ultimately the goal of all aging research, she said.

“The naked mole rats age in a very healthy way,” she said. “And evolution created such a rodent. We can achieve something like that if we do enough research.”

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