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The bizarre biology of the naked mole rat means oxygen is a bonus

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Scientists have just discovered it’s because of a weird metabolic switch

Photo by Thomas Park, UIC (press release image) Photo by Thomas Park, UIC

Naked mole rats are tough creatures — they can withstand cancer, pain, and even survive 18 minute stretches without any oxygen. And now, scientists have a better idea of how the super rodents can survive that long without suffocating. The findings, published today in the journal Science, could one day help researchers figure out how to keep humans healthy when oxygen gets cut off by strokes or heart failure.

Naked mole rats are wrinkly, hairless, poop-eating, delightful creatures that live in large colonies of up to 280 animals. They spend their lives crawling through tunnel networks beneath the deserts of Africa — where the air can get a little stuffy, and very low on oxygen. On the surface, carbon dioxide makes up less than one percent of the gases we breathe. But in these tunnels, carbon dioxide can account for 7 to 10 percent of the warm, close air.

Photo by Jane Reznick and Gary Lewin, MDC (press released) Photo by Jane Reznick and Gary Lewin, MDC

For most creatures, these conditions would be unlivable. We need oxygen to survive, because oxygen is key for generating the energy our bodies rely on to function. Cut off the oxygen, and we humans start hyperventilating, panicking, and having acid build up in our tissues. In the long run, we can experience serious brain damage, or even death.

But even if oxygen is low, the naked mole rats are … fine. And scientists wanted to understand how that’s possible. So, after getting approval from an ethics committee, the researchers put naked mole rats in atmospheric chambers — basically, sealed tubes — and started dialing back the oxygen levels. They saw that, even when oxygen levels dropped to just five percent of the gases in the tube (atmospheric oxygen levels are typically closer to 21 percent) the rats were fine for five hours. Mice, by contrast, suffocated and died after just 15 minutes.

Photo by Roland Gockel, MDC (press released)
Naked mole rats, at home in their tunnels
Photo by Roland Gockel, MDC

When the oxygen was completely removed and replaced with nitrogen, the mice died after 45 seconds. The naked mole rats passed out. But even after 18 minutes of no oxygen, they recovered when they were put back in normal air. (30 minutes of no oxygen was another story — they died.)

So how do the naked mole rats do it? Apparently, the rodents go into a kind of suspended animation, which reduces their little bodies’ energy demands. What’s more, the researchers discovered that fructose levels rose in the naked mole rats’ tissues compared to in mice. They also found pumps that funnel fructose into cells in the heart and brain — whereas in mice, these pumps are mainly in the kidneys. That suggests the naked mole rats switched to a kind of oxygen-free metabolism that relied on fructose, instead of glucose.

Photo by Roland Gockel, MDC (press released)
Naked mole rats like to snuggle, which is one reason it can get so stuffy in their tunnels.
Photo by Roland Gockel, MDC

By switching to fructose, naked mole rats can keep producing energy needed by vital organs to survive. The problem with this kind of oxygen-free metabolism is that it can cause toxic byproducts to build up in the muscles. These toxins need to be released, or buffered, somehow, but the researchers don’t know how that happens yet. They also don’t know which organ is storing and releasing the fructose — that’ll be for future studies.

But the hope is that this information will one day help scientists figure out how to mimic the same mechanism in humans who are suffering from stroke or heart failure. These conditions cut off oxygen to vital organs and can be fatal.

For now, though, this helps us understand yet another way that naked mole rats are superior creatures — despite their appearance. “[E]very aspect of naked mole-rat biology seems to be unusual and bizarre in some way,” write the authors of a commentary published alongside the study. “It is perhaps not surprising that they have evolved a particular means of tolerating low oxygen conditions.”

Look at that little face
Photo by Roland Gockel, MDC