If you take away a mouse's oxygen, the mouse is going to die within 20 seconds. If you take away a naked mole-rat's oxygen, though, it will be fine for up to 18 minutes.
Naked mole-rats are marvelous and bizarre rodents, arguably the world's weirdest mammals. The East African critters do not get tumors. They're immune to types of chronic pain and the irritant in chili peppers. They live like social insects, in 300-strong underground colonies where a mole-rat queen gives birth to worker children (the offspring themselves will never bear young). Though the mole-rats are mammals, they do not internally regulate their body temperature — they are coldblooded, so to speak, in the manner of frogs. Mice live a maximum of three years. Old Man, the world's oldest mole-rat, died at 32.
And naked mole-rats thrive in oxygen-poor air, even at levels that would be lethal to mice or humans. If the naked mole-rats behave like a strange medley of wrinkled rodent, termite and toad, throw vegetable into that mix, too: When oxygen is scarce, as scientists report Thursday in the journal Science, the mole-rats switch their energy source from glucose — what humans and virtually all other mammals use — to fructose. That's the sugar that plants use.
The air you're breathing right now is, in all likelihood, just about 21 percent oxygen. The Occupational Health & Safety Administration defines “oxygen-deficient” air as less than 19.5 percent. Humans, unless they go through a careful acclimation process, stop functioning well at around 10 percent. Thrust into a cage with air at 5 percent oxygen, humans would die.
When Thomas Park, an expert on naked mole-rats, placed the first animal in a chamber containing only 5 percent oxygen, the mood, he said, was “tense.” The scientists began their stopwatches and waited for the slightest twitch of distress. The animal, though, seemed unaware that three-fourths of the oxygen in its environment had vanished. Fifteen minutes passed. The animal was unperturbed. Minutes bled into hours. The scientists called time after 300 minutes.
“They didn’t even go to sleep,” Park, a University of Illinois at Chicago neurobiologist and co-author of the new study, told The Washington Post.
The researchers tested the animals at even less oxygen: 0 percent. The mole-rats fell into a sort of suspended animation while totally oxygen-deprived. Their heart rate dropped from 200 beats per minute to about 50. Once the scientists added oxygen back into the mole-rats' atmosphere, the rodents made a swift recovery.
“They were able to survive up to 18 minutes without any apparent neurological damage,” said Jane Reznick, a study co-author and molecular biologist at the Max Delbrück Center for Molecular Medicine in Berlin.
Scientists knew that naked mole-rats could get by without much oxygen. Previous research indicated that the mole-rats' red blood cells, which transport oxygen, sported an ultra-sticky version of hemoglobin that seems to make the cells extra efficient. The oxygen in the mole-rat's tunnels may dip as low as 8 to 10 percent, Park said. No one has been able to probe the air in their crowded subterranean nests, where the oxygen may dive even lower.
What Park did not expect were the fructose molecules flooding the bodies of the oxygen-deprived rodents. Using a technique called mass spectrometry, Park and his colleagues analyzed tissue from the mole-rats' vital organs, including their brains and hearts. They tuned the spectrometer to search for hundreds of different metabolites.
“Boy, that was a big pile of data across the desk,” Park said. But the researchers didn't need to spend a long time sifting. “The fructose curves just jumped out.”
Like glucose, fructose is a sugar. But organisms that turn fructose into fuel — plants, and the mole-rats — do so without requiring oxygen as a key metabolic component.
Human brains, of course, need oxygen to live. “We’ve put all of our chips into the glucose pathway,” Park said. Though our cells have the genetic information required to build the fructose pathway, those are mostly inactive in vital organs like brains and hearts. For us, our livers process fructose into what eventually ends up as fat cells.
But, because our cells have that information, Park has to wonder: “In a time of crisis, could we turn ourselves a little bit into naked mole-rats?”
The idea that scientists can transform naked-mole-rat biology into human therapy is still fairly speculative. Park noted that the mole-rat is still little-studied as an animal model. Scientists discovered their unusual pain tolerance as recently as 2009, and researchers have only had their genome sequence since 2011. He envisioned that this research could be a launching point for other neurobiologists and scientists. (Another intriguing finding: mole-rat lungs do not fill with fluid when deprived of oxygen, a severe symptom called pulmonary edema suffered by some high-altitude mountain climbers.)
The mysteries of the naked mole-rats will continue. “We still don’t know where the fructose comes from,” Reznick said. Perhaps the mole-rats have some sort of fructose storage system. If the rodents' bodies somehow produced fructose, that would be even stranger. But it's hard to rule out oddity when it comes to the mole-rats.