Naked Mole Rats and the Secret to Longevity

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 SAN DIEGO (April 28, 2014) – Zoo-goers may marvel at their bare skin and wrinkles, but scientists are more interested in the long lives of the pale, toothy and nearly hairless rodents known as naked mole rats. With lifespans of up to 31 years, naked mole rats live decades longer than would be expected based on their size. By comparison, mice live at most four years.

A new study links the naked mole rat's remarkable lifespan to a molecular chaperone protein known as HSP25. HSP25 and other chaperone proteins act like a tiny quality-control team within an animal's cells, quickly eliminating incorrectly manufactured or damaged proteins before they can cause a problem. Researchers say understanding changes in the actions of HSP25 during aging could shed light on age-related diseases like Alzheimer's and Parkinson's.

"Using a variety of rodents, we found that the amount of HSP25 present in their tissues positively correlated with the animal's maximum lifespan," said Karl Rodriguez, Ph.D., a postdoctoral fellow at the University of Texas Health Science Center at San Antonio who conducted the experiments. "If we can understand how HSP25 levels are regulated, what its function is and how it contributes to cell health, we might find ways to use this protein to combat devastating age-related diseases."

The researchers compared HSP25 levels in naked mole rats to levels of the protein found in rodents with different maximum lifespans, from mice (four years) to guinea pigs (12 years) to Damaraland mole rats (20 years) and others in between.

"In animals with higher levels of HSP25, having more of these quality-control proteins means they are primed to react when there is a problem, so they can quickly transport the faulty protein to cellular garbage dumps and maintain the health of the cell," said Rodriguez.

Many neurodegenerative diseases, including Alzheimer's, Parkinson's and prion diseases, are caused by defective proteins that are allowed to proliferate and accumulate into dangerous structures called aggregates. Finding ways to safely increase a person's level of HSP27 (the human corollary to HSP25) could potentially help to prevent or treat such diseases, said Rodriguez.

Native to the horn of Africa, naked mole rats live underground in colonies with complex social structures akin to those of ants or bees. In addition to their noted longevity, they are remarkably resistant to cancer.

Naked mole rats also appear to remain spry and healthy even in the final years of their long lives, so they can potentially offer clues not only about longevity but also the overall maintenance of health.

The study offers unique insights into the role of a previously poorly-understood protein in the context of aging of a naturally-evolved species, said Rochelle Buffenstein, Ph.D., the study's senior investigator and a professor of physiology at the University of Texas Health Science Center at San Antonio.

"There's still a lot we can learn from extremely long-lived animals. Use of such models enables us to evaluate whether nature—through millions of years of evolutionary experimentation—has already evolved the best way to maintain cellular integrity and thereby delay and attenuate the aging process. HSP25 may be one such evolved protein," Buffenstein said.

Karl Rodriguez will present the findings during the Experimental Biology 2014 meeting on Monday, April 28 from 12:45 – 3:00 p.m. at the Comparative Physiology of Aging and Senescence poster session in Exhibit Halls A-D (Poster #A317) and on Monday, April 28 from 4:30 – 4:45 p.m. at the Comparative Physiology of Aging and Senescence featured topic session in Room 25C, San Diego Convention Center. 
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