Genome of Cancer-Free Rodent May Give Clues to Human Aging, Disease

Naked mole rat, humans share some genetic similarities, researchers find

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Genes and Gene Therapy

WEDNESDAY, Oct. 12 (HealthDay News) -- Scientists announced Wednesday that they have succeeded in sequencing the full genome of the naked mole rat, an exceptionally long-lived and cancer-resistant rodent.

While that might not sound like headline news, scientists say the findings could provide insights into human aging and risks for malignancy.

"If we can understand the genetic adaptations, we may be able to find treatments which can change the human into a more long-lived species," said Vadim N. Gladyshev, senior author of the study published online Oct. 12 in the journal Nature.

Another expert, Dr. Greg Enders, associate professor of medicine at Fox Chase Cancer Center in Philadelphia, expressed enthusiasm. "This paper is an interesting piece of work [and may provide] useful hypotheses into how they can have such longevity and not cancer."

However, these ideas are still "all hypothetical in the future and very controversial," added Gladyshev, director of the Center for Redox Medicine at Brigham and Women's Hospital and Harvard Medical School in Boston.

On average, the naked (meaning hairless) mole rat lives more than 30 years, or almost 10 times as long as a typical mouse. Not only are they healthier for a longer period of time than other rodents, they live underground in the dark, are cold-blooded and can reproduce until they die. They do have poor vision, however.

"They have many unusual traits, and all of them are important in some way," said Gladyshev. "They are long-lived, live in low-oxygen conditions, are resistant to cancer, [and] don't maintain a stable body temperature."

In analyzing the genome of this remarkable mammal, the researchers noted some similarities with other mammals. The number of genes is about the same in naked mole rats (22,561), humans (22,389), mice (23,317) and rats (22,841).

Many of the naked mole rat genes are also located in the same place on the chromosome as human, mice and rat genes, the research revealed.

But in the naked mole rat, unlike in humans, there were few differences in how the genes were expressed at age 4 and at age 20.

There were eight cancer-related genes, one of which was the protein P16. "This is one of the major human tumor suppressor proteins, and it's clear that the naked mole rat has that protein and upregulates it more rapidly in certain situations that probably prevent cancer formation," Enders said.

The naked mole rat also produces less insulin than humans, has adapted its circulatory system and metabolism to deal with a low-oxygen environment and has few of the receptors that detect bitter tastes. These adaptations may eventually yield clues about living in extreme conditions, the researchers noted.
This research is just a start, Gladyshev said. "We and others probably will now carry out experimental studies on some of these findings to really understand in detail what this data means."

SOURCES: Vadim N. Gladyshev, Ph.D., director, Center for Redox Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston; Greg Enders, M.D., Ph.D., associate professor of medicine, Fox Chase Cancer Center, Philadelphia; Oct. 12, 2011, Nature, online

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