Breathing Less Oxygen Reduces Jet Lag, At Least In Mice

Whether it's jet lag, a new work schedule, daylight saving time or just a Monday morning, shifting sleep schedules takes a toll. But scientists think they might have found a way to reset our internal timers that's more than hot air.

At least, it works if you're a mouse. The solution, it seems, is thin air. A study published Thursday in the journal Cell Metabolism found that decreasing oxygen levels for a short period of time helped mice recover from jet lag faster.

According to Dr. Gad Asher, a clinician and assistant professor at the Weizmann Institute of Science in Rehovot and lead researcher on the study, this is because of our circadian clocks, molecular pathways that tell us when to sleep, move and eat. Scientists think these clocks are present in almost every cell in our body.

"If there are so many clocks, how do they all show the same time?" Asher wanted to know. Researchers had already identified a few universal clock resetting cues, including temperature. When we sleep, our body temperature drops. Because all the cells in our body use oxygen, Asher thought oxygen levels might be another cue.

First, Asher and his team put a bunch of mice in special cages designed to measure oxygen consumption and used a monitor to track their blood oxygen level. They found that the amount of oxygen the mice used rose and fell over the course of the day.

Then, they gave a bunch of mice jet lag — not by putting them on an airplane, but by moving their light-dark cycle up by six hours to throw off the brain's clock. When they exposed some of the mice to 12 hours of decreased oxygen before the shift, or two hours after, the mice adapted to their new light-dark cycle much faster.

Asher also wanted to identify which proteins helped these circadian clocks sense the changes in oxygen levels. He chose HIF1α, a protein that helps cells know when and how to use oxygen. The researchers knocked out one set of HIF1α genes in a group of mice and repeated the experiment. Low oxygen didn't help cure jet lag in the mice without HIF1α.

"It's not shocking, exactly, that oxygen is involved in circadian rhythm. But I don't think it was ever established before now," says John Hogenesch, a professor of pediatrics at Cincinnati Children's Hospital Medical Center and circadian rhythm researcher who was not involved in the study. "And it's great that they show HIF1α is involved, though I think we'll find there's more to it than that."

Because HIF1α is involved in a lot of different cell processes, Hogenesch hopes this research could help scientists understand some of the negative consequences of long-term fatigue and working night shifts. But there's still a lot more work to do first.

"One big question is: Is this oxygen-resetting mechanism unique to mice? To mammals? Or is it present in all organisms?" says Asher.

Assuming the results of this study hold true in humans, there are still more things Asher would like to know. For example, does changing the oxygen level work best before, during or after a flight? Would you need to be exposed multiple times, or is once enough to treat the tired? Does raising oxygen have the same effect as lowering it?

Still, Asher imagines a future where passengers might step off an airplane and into an oxygen bar, sipping O₂ while they wait for their bags to be unloaded. Or, perhaps, oxygen masks will drop as a plane descends (in first and business class only — coach can caffeinate their way through circadian delay like they always have) and people will disembark bright-eyed and well-adjusted to their new time zone.

And there are other, more practical applications of this research, Hogenesch points out. Jet-lagged jet-setters aren't the only people whose internal clocks are out of whack.

According to the Bureau of Labor Statistics, 21 million Americans work night shifts, evening shifts, or have shifting work schedules that sometimes include evenings or nights.

Working an irregular schedule doesn't just make someone sleepy, says Hogenesch. Fatigue from shift work is associated with a suite of health impacts, including heart disease, obesity and diabetes. And working while fatigued can increase the risk of on-the-job injury.

There's still a long way to go to find out whether manipulating oxygen levels could ever become a treatment for the impacts of shifting circadian rhythms in humans.

But mouse and rat sightings on airplanes are pretty common, so frequent-flying rodents can rejoice! A cure for their jet lag, at least, may be on the way.