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

Say what you will about naked mole-rats but their bodies have a trick that lets them survive periods of oxygen deprivation

"The naked mole rat has simply rearranged some basic building-blocks of metabolism to make it super-tolerant to low oxygen conditions", said Thomas Park, professor of biological sciences at the University of IL at Chicago, who made the discovery after studying the species for 18 years.

Now the East African rodent turns out to have a metabolic trick that allows it to survive very low oxygen levels with no apparent ill effects. The rodents are freakish in just about every way. They can live more than 30 years, are cold-blooded, have a social hierarchy comparable to bees or ants, can run backwards and forward with equal ease, eat their own poo, can move their teeth individually like chopsticks and are one of the strangest looking creatures on the planet.

Park said the study just scratches the surface of what researchers need to know for humans to survive oxygen deprivation.

"You and me and all the other animals in the world use a sugar called glucose, and glucose is really good", Thomas Park, lead author of the study and professor of biological sciences at the University of IL at Chicago, told Gizmodo. As a result, the air in these confined, packed spaces is often 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.

Not so for a hairless, underground rodent called the naked mole-rat. They also appear to be largely immune to cancer, with the first case of the disease in a naked mole-rat only confirmed in 2016.

"So we put them in the chamber and after five minutes, nothing". "What I've experienced over and over again is people will say, 'Oh, they're ugly, they're gross, ' every single person that I've taken to actually see the mole rats in person has come away saying they're cute and they're lovable", Park said. An hour later, there were still no problems. Findings showed that while the mice died in fewer than 15 minutes, the naked mole-rats could survive for five hours.

"It's not that they've invented something new, they've just exaggerated a pathway we mostly don't ever need to use", Park said of the rats' metabolic pathways, or process for converting energy.

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

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"If we could activate the fructose pathway in a heart attack victim, that would extend the amount of time we have to get that victim to a medical facility where they can get resuscitated and spare the brain damage that frequently comes along with a heart attack", Park said. Compared to the atmosphere's oxygen level of 21 percent, in naked mole-rat tunnels oxygen can drop to as low as 6 percent.

"And that was a surprise, too", he says. This suffocating experience would kill a mouse-a mammal of similar size, albeit with significantly more hair.

In aerobic metabolism, which the body normally relies on, the mitochondria (the cell's batteries) use broken-down glucose and oxygen to produce a molecule called ATP, which biologists call the cell's energy currency.

"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. This suggested that the brains switched their power source to fructose from glucose during a lack of oxygen.

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.

Better understanding the mole rat's energy switchover will be key to any hope of somehow using it to help humans. According to McClelland, even fish or turtles that can survive long periods without oxygen have not modified glycolysis in that way.

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.

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.

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