May 1, 2017
Blog by John Mangels
Science Communications Officer
If you’ve been to the Cleveland Museum of Natural History’s Amazing Species exhibit, you know about African naked mole rats. They’re those shockingly hairless, seriously bucktoothed, furiously burrowing rodents whose social structure of workers, soldiers and queens is more akin to insects than mammals.
Naked mole rats are also known for their pain tolerance, longevity, and virtual freedom from cancer. (Those latter two qualities may be linked, and are the focus of lots of research.)
Now there’s another reason to consider them amazing.
New research shows that naked mole rats can survive for hours in extremely low-oxygen environments, and can live for as long as an astonishing 18 minutes without any air at all. The findings may eventually pay off in heart attack and stroke treatments.
The extreme adaptations, called hypoxia tolerance and anoxia resistance (hypoxia means low oxygen; anoxia is the absence of it) are essential for naked mole rats’ well-being, because they live underground, packed together in burrows occupied by as many as 280 animals. There’s lots of breathing going on, but little fresh air.
In those cramped subterranean quarters, oxygen levels may plummet from the normal 21 percent to 6 percent, while the amount of carbon dioxide — the waste gas that air-breathing animals exhale — can reach 7 to 10 percent, far higher than in surface air. Without biological mechanisms to cope with low or no oxygen, naked mole rats would die.
With so many bodies crammed in such a small area, the animals also have to cooperate.
“One of the coolest things about naked mole rats is that being good-natured is in their genes,” says University of Illinois at Chicago neuroscientist Thomas Park, Ph.D., who co-led the study. “They evolved to live in very large colonies, which is critical to finding enough food. They dig in teams, searching for potato-like roots that are scattered here and there. But to make this system work, the colony members have to be community-minded. When one digging team finds a root, they share with the entire colony. Also, they are constantly bumping into one another in the cramped tunnels. If they were not good-natured, there would be a lot of scuffles.
“As a result of their good-natured personalities, they are willing to be handled in the lab without complaining,” Dr. Park says. “They may be a little scary to look at, but they are some of the nicest animals to work with.” 
Slowing Metabolism
Hypoxia tolerance and anoxia resistance aren’t unique to naked mole rats.
Many creatures have developed ways to limit energy use by slowing breathing, heartbeat and blood circulation, allowing them to survive challenging conditions, particularly winter’s cold. Hibernating bears only inhale about once a minute. Bats are able to live in suspended animation for as long as six months, during which they cut their oxygen intake by nearly 98 percent.
Some species can go to even greater extremes. By dramatically lowering their metabolism and body temperature, North American freshwater turtles and Eurasian carp and goldfish can survive several months with no oxygen at all while buried in mud beneath a frozen pond.
Humans, by contrast, lose consciousness and suffer permanent brain injury or death after just a few minutes without air. Our large, energy-hungry brains are especially vulnerable to oxygen deprivation.
Naked mole rats aren’t hibernating when they’re underground, though. It’s their normal living environment, so they aren’t doing anything to reduce their activities. But they don’t seem to be bothered by extended periods of low oxygen levels, or hypoxia. And they can tolerate minutes of anoxia, or zero oxygen, without apparent harm.
Coping Without Oxygen
To find out how, Dr. Park and the international team of researchers first tested the naked mole rats’ endurance compared with mice while controlling the amount of oxygen they breathed in an atmospheric chamber.
The naked mole rats did fine breathing air containing only 5 percent oxygen for five hours. The mice died in less than 15 minutes.
In a zero-oxygen atmosphere, the naked mole rats and mice each lost consciousness in less than a minute. After 60 seconds of anoxia, none of the mice recovered when normal oxygen levels were restored. But the naked mole rats rapidly rebounded after as long as 18 minutes without oxygen, with no signs of brain or behavioral problems.
Unlike the mice, which quickly stopped breathing in anoxic conditions, the naked mole rats kept trying to breathe for as long as 7 minutes. All of the rodents’ heart rates dropped sharply without oxygen, but while the mice heartbeats eventually stopped, the naked mole rats maintained a steady 50 beats per minutes, about one-quarter of their normal rate. 
Alternate Ways to Make Energy
The heart, lungs, brain and other vital organs of living things require energy to function. Most mammals derive that energy from glucose, a simple sugar found in food. A chemical process breaks down glucose and produces ATP, a molecule that transports energy within cells to keep them working.
Oxygen from breathing is the most efficient way to break down glucose and produce ATP. The turtles and fishes that don’t breathe for months in frozen ponds stay alive by drastically lowering their metabolism, storing large amounts of glucose and using a non-oxygen method to convert it to energy. But that process doesn’t generate as much ATP and can stop under certain conditions.
Naked mole rats have evolved a different, potentially better way to keep churning out ATP with little or no oxygen, Dr. Park and his colleagues discovered. They’ve rewired their bodies to be able to switch from glucose to fructose, or fruit sugar, to make vital energy to sustain brain and heart.
Fructose-based metabolism isn’t subject to the sudden stoppages that can happen with non-oxygen glucose metabolism, so it’s more reliable and could help explain why naked mole rats’ hearts are able to keep beating and brains remain unharmed during many minutes without oxygen.
Normally, mammals only break down fructose in the liver and kidneys. But naked mole rats have developed ways to move fructose into their brain, heart and lung cells, and to process it there, where it’s needed most. Understanding that capability and replicating it could potentially help in medical emergencies.
Like naked mole rats, humans have the ability to metabolize fructose for energy, Dr. Park notes. “The only difference is that the naked mole rat’s brain cells have much more of the fructose transporters and enzymes compared to our brain cells. When a person suffers a severe heart attack or stroke, they only have a few minutes to reach medical help before their brain cells run out of energy and begin to die. The goal now is to figure out how to up-regulate these parts of the fructose pathway in a heart attack or stroke situation. This would extend the time window for reaching help to many minutes or even hours.”
Science writer John Mangels is The Cleveland Museum of Natural History’s science communications officer. Contact him atjmangels@cmnh.org.
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