Researchers Find Yet Another Reason Why Naked Mole-Rats Are Just Weird

Enlarge this image toggle caption Roland Gockel/Max Delbruck Center for Molecular Medicine Roland Gockel/Max Delbruck Center for Molecular Medicine

Animals, especially mammals, need oxygen to keep their bodies and brains humming along.

But leave it to the African naked mole-rat to buck that trend. The rodents are bizarre in just about every way. They're hairless, ground-dwelling and cold-blooded despite being mammals. Now, scientists report in the journal Science that the animals are capable of surviving oxygen deprivation.

"They have evolved under such a different environment that it's like studying an animal from another planet," says Thomas Park, a neuroscientist at the University of Illinois at Chicago.

He and his colleagues knew that naked mole-rat bodies work differently than those of other mammals.

For example, instead of generating their own heat, they regulate body temperature by moving to warmer or cooler tunnels, which lowers the amount of energy they need to survive. They're also known to have what Park calls "sticky hemoglobin," which allows them to draw oxygen out of very thin air. And because they live underground in large social groups, they're used to breathing air that's low in oxygen and high in carbon dioxide.

Park and his colleagues wondered if they animals had another trick up their (nonexistent) sleeves for handling such extreme conditions.

"We were thinking, 'Gee, if you put all these things to bear on the problem of surviving in low oxygen, just how far can you go?' " Park says. "And the naked mole-rats surprised everybody, I think."

To start out, he and his colleagues tested how well the mole-rats fared in a chamber with only 5 percent oxygen, which is about a quarter of the oxygen in the air we breathe, and can kill a mouse in less than 15 minutes.

They watched closely, ready to pull the mole-rats out at the first sign of trouble.

"So we put them in the chamber and after five minutes, nothing. No problems," Park says. An hour later, there were still no problems.

Five hours later, the researchers were tired and hungry and ready to go home, but the mole-rats could've kept chugging along.

"Oh, I think so," says Park. "They had more stamina than the researchers."

The animals had slowed down a bit, he says, but were awake, walking around and even socializing.

"They looked completely fine," he says.

Next, the researchers decided to see how the mole-rats dealt with zero percent oxygen.

"And that was a surprise, too," he says.

Such conditions can kill a mouse in 45 seconds.

The four mole-rats involved in this leg of the study passed out after about 30 seconds, but their hearts kept beating and — a full 18 minutes later — the mole-rats woke up and resumed life as usual when they were re-exposed to normal air. (The three mole-rats that were exposed for 30 minutes, however, died.)

According to Park and colleagues across three continents, the rodents do have a trick up their sleeves.

Most mammals, including humans, run on glucose, which is a sugar that the digestive system gets from our food and turns into energy to keep our bodies warm and our brains running. But the process of taking that sugar and turning it into energy requires oxygen. Without oxygen, the body can't create energy, and without energy, cells die.

When the researchers looked at tissue samples taken from the mole-rats at various times during the oxygen deprivation, they noticed a spike in levels of another sugar, fructose, about 10 minutes in.

"We weren't looking for it, but bang, fructose goes way up in the blood and then it goes way up in the organs and it gets used by heart and brain," Park says.



The naked mole-rats appear to have the option of switching fuels from glucose, which requires oxygen to create energy, to fructose, which doesn't.

(It's the same "fructose" as the one in "high-fructose corn syrup," an ingredient implicated in a number of health problems in humans. "Normally we think of it as a bad thing," Park says.)

Humans are capable of storing and using fructose in the liver and kidney, but as Park explains, we don't have enough of the correct enzyme to create energy directly from fructose. Nor do we have enough of the proteins necessary to move fructose molecules into the cells of vital organs. Our cells have to convert it into glucose in order to use it.

The cells in the brain, heart, liver and lungs of naked mole-rats are all outfitted with proteins that moves fructose into the cells, and with the right enzyme to create energy from it.

"They have a social structure like insects, they're cold-blooded like reptiles, and now we found that they use fructose like a plant," Park says.

Some fish and turtles manage to manage to survive without oxygen for months, sealed in frozen ponds and lakes.

But Jay Storz, an evolutionary physiologist at the University of Nebraska who researches how animals adapt to extreme conditions, says those creatures still use glucose to fuel themselves. They just drastically reduce their energy needs.

The naked mole-rat's ability to switch tracks to a different metabolic fuel is really surprising. "They're doing something that really has not been described before for any vertebrate animal," Storz says. "They're basically using an alternative fuel."

One question for future research, he says, is how the animals manage to get rid of lactate, a molecule that builds up during anaerobic metabolism and can alter blood chemistry.



Park and Storz hope that the finding about naked mole-rats could someday help develop a way to aid patients suffering from oxygen deprivation from something like a heart attack or stroke.

"It would be great if we could beef up the fructose pathway in those patients and extend the amount of time that they have to get to a health care situation," Park says.

Storz imagines mole-rats aren't the only extreme animals with potential clues to alleviating human medical problems.

"There are probably a lot of other animals out there that are doing equally bizarre things," Storz says. "There's a lot of research and development that evolution has done, and we just have to figure out ways to capitalize on that."

But that, they say, is a job for scientists in another field.