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Key to naked mole rat longevity may be related to their body's ability to make proteins accurately

NMRNaked mole rats have achieved a kind of celebrity status in my mind. If they had nothing else going for them, these nearly hairless, Twinkie-sized, subterranean, social rodents would be fascinatingly quirky to me. But they're also resistant to cancer and, with an average lifespan of ten to thirty years, remarkably long-lived. So, I expected a certain "wow" factor when I settled into my blanket to read a recent study on why naked mole rats live so long.

I wasn't disappointed.

Until recently, little was known about how, or why, naked mole rats have such long lifespans. Now, scientists have uncovered a clue that could explain why naked mole rats live longer than other animals their size: They're exceptionally good at making perfectly assembled proteins.

Proteins are assembled in chains much like a person would string popcorn with a needle and thread. If you’ve ever strung popcorn, you know that your hands don’t always grab the best popcorn pieces. In a similar way, the part of the cell that assembles proteins, called the ribosome, can make mistakes when grabbing and matching tiny protein pieces to the blueprint it uses, called messenger RNA, to assemble a protein strand.

According to the research team, led by the husband and wife duo Andrei Seluanov, PhD and Vera Gorbunova, PhD, naked mole rat ribosomes may excel at assembling proteins because they have a mutation that changes their shape. In naked mole rats, a specific region of the ribosome is made up of two pieces instead of one. This could change the way it selects and assembles protein pieces when making a protein strand.

These findings are important, the research team writes, because our body's ability to accurately make and fold proteins is known to affect the aging process and how long we live.

The results of their study are detailed in the journal Proceedings of the National Academy of Sciences. Carl Zimmer, provides a tidy summary of how the study was done on his blog, The Loom.

From Zimmer's blog:

The researchers compared how the naked mole rats make proteins to the process in mice. They engineered a gene and inserted it into both species. If a cell made an error at one site in the protein, the protein would give off a flash of light. A cell that always built perfect proteins would stay dark. A sloppy cell would glow.

The scientists found that the naked mole rat cells were much darker than those of mice. They built the engineered protein far more accurately, in other words. Naked mole rats, the scientists found, made anywhere from four to ten times fewer mistakes. Yet the naked mole rats can make their proteins as quickly as the sloppier mice.

The researchers cannot yet state with certainty that naked mole rats are able to make perfect proteins because of the mutation in their ribosomes. Nor can they say that this mutation is the reason why naked mole rats tend to live so long. This work is the research team's next project. But, as the research team states in their press release, they hope that someday these results can be used to improve drug treatments that correct protein assembly in humans.

Holly MacCormick is a writing intern in the medical school’s Office of Communication & Public Affairs. She is a graduate student in ecology and evolutionary biology at University of California-Santa Cruz.

Previously: How structural biology provides insight into health and diseaseHow play and games can impact the future of science and healthPotential therapeutic target for Huntington’s disease discovered by researchers in Taiwan, Stanford and New insights into protein folding could aid in developing therapies for neurodegenerative diseases
Photo by Adam Fenster/University of Rochester

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