Naked mole-rats in Thomas Park's laboratory. (Credit: Thomas Park/UIC) Though they may look ugly to us, naked mole-rats never want for friendship. The hairless rodents live in large colonies under the earth, inhabiting byzantine warrens under the soil of their native East Africa. They send foraging parties out through the dirt in search of the tree roots and tubers that sustain them, and when it comes time to rest, they gather together in a massive pile to sleep. Their isolation offers security, but being cut off from the surface poses its own dangers. Even basic essentials, like oxygen, are in short supply underground. Naked mole-rats are hardy creatures though, and their subterranean preferences have occasioned some intriguing evolutionary divergences. They are cold-blooded, for starters, rarely get cancer, live decades longer than other rodents, don't feel most kinds of pain and, as a new study from an international team of researchers shows, they can survive without oxygen for up to 18 minutes.
Look Ma', No Oxygen
Led by Thomas Park, a professor of biology at the University of Illinois at Chicago, a team of researchers from the U.S., England, Germany and South Africa found that naked mole-rats use an unconventional biological mechanism to sustain themselves in the absence of oxygen. When faced with anaerobic conditions, they use fructose stored in their bodies to power brain and heart cells — the same kind of mechanism that plants use. When oxygen is once again available, they switch back to normal metabolism with no evidence of harm. Park's lab has worked with naked mole-rats for 18 years now, and he had been steadily picking up on clues that the rodents could survive oxygen deprivation during the course of his research. For starters, the simple fact that they live underground, where oxygen is in short supply, was a big hint that they possessed unique abilities, he said. In addition, they are cold-blooded, so they don't need to use energy to keep themselves warm. Their hemoglobin is also especially good at grabbing oxygen molecules, allowing them to make do with much less than, say, a human. Still, because experiments of this sort had never been tried before, Park had some reservations about starving his subjects of oxygen. "We were a little bit nervous about it because we decided to see what would happen if we put a naked mole-rat in five percent oxygen," he says. "We knew a five percent oxygen would be deadly for humans and for laboratory mice, so we were kind of ready to abort this experiment right at the beginning. And we put them in and fifteen minutes later they looked fine, after an hour they looked fine, and after five hours of exposure to five percent O2 they still looked fine, so we called it a day at that point and said we're just going to arbitrarily say they can go five hours or more." Once those experiments were successful, they were confident enough to try it with even lower levels, and found that naked mole-rats don't actually need any oxygen to survive, if only for short periods of time. They published their findings Thursday in Science.
The air we breathe is normally composed of around 21 percent oxygen, and even on the top of Mount Everest, where climbers must bring oxygen tanks to survive, oxygen levels are only about a third of what they are here. Mice exposed to conditions of five percent oxygen died within 15 minutes, and humans likely wouldn't make it much longer without incurring lasting damage. Thanks to their unconventional biology, however, the naked mole-rats survived totally unharmed. They can do so because they possess a kind of backup system that can run entirely without oxygen. In our cells, oxygen is the fuel that converts stored glucose into energy that our bodies can use to power hearts, lungs and brains. Cut off from our supply, we die within minutes. Naked mole-rats normally function the same way, drawing on oxygen to tap into glucose reserves. But, when the oxygen disappears, they are able to turn to another sugar, fructose, to accomplish the same task. Looking at cells from naked mole-rat brains and hearts, the researchers found that they were covered in fructose transporters, necessary for getting the molecules into the cells. Once inside, specialized enzymes turn the fructose directly into energy, Park says, taking up the slack where glucose is unavailable. That's not all that goes on when they run out of oxygen, however. As their cells are ramping up to turn fructose into energy, their bodies are powering down, entering what Park says looks like "suspended animation." Their heartbeats drop from around 200 to 50 beats per minute, respiration levels drop, and they stop moving around to conserve energy. The goal is to be as efficient as possible to get the most out their fructose reserves. Our bodies can actually do the same thing with fructose, except not nearly at the same scale. Our kidneys and livers possess fructose transporters similar to those of naked mole-rats, which allow us to metabolize the high-fructose corn syrup beverages we enjoy so much. We don't possess the same kind of transporters elsewhere, however, and even in our digestive systems, we're not very good at converting fructose to energy. Fructose has come to have such a bad name today only because our bodies are so bad at metabolizing it in comparison to glucose. "We can't directly use it for energy except at very, very low levels, so most of our fructose has to go through several other conversions before it's usable," Park says. In humans, high levels of fructose are usually associated with cancer, heart failure and metabolic syndrome. It's likely that naked mole-rats' eccentric living habits allowed them to turn something unhealthy into a lifesaver. Park says he hopes that his findings could be used one day to help save heart attack and stroke victims by prolonging the amount of time they can go without blood flow. Because we already have the ability to turn fructose into energy, just like the naked mole-rats, we could one day upregulate these mechanisms and potentially use them to sustain critical tissues without oxygen.