During the pandemic, many people barely left their neighborhoods, let alone their own time zones. But vaccines are available, cabin fever is rampant, and the holiday travel season is upon us. And so, inevitably, is jet lag.
The human internal time-keeping apparatus, known scientifically as the circadian clock, is a powerful force. It synchronizes functions across organs and tissues, and affects cognitive function, digestion, sleep, and even asthma. Adjusting the circadian clock to a new time zone or schedule isn’t as simple as resetting a wristwatch, but current research about how to manipulate it can be helpful for anyone, whether they’re traveling to their in-laws’ house or to Mars.
“There’s so much promise coming forward, now that we understand the molecular power of the clock, to harness the power of the clock for good,” says Carrie Partch, a professor of biochemistry at UC Santa Cruz who studies the circadian system. She says the more we understand about the clock, the more freedom we’ll have, because we can make it an ally rather than a foe.
Throughout the body, cells have their own circadian clocks that regulate metabolism and other cellular functions. Those clocks coordinate between other cells in specific organs and even between organs—though how they do that is something scientists are still trying to figure out. All of these individual clocks are regulated and synchronized by the brain’s suprachiasmatic nucleus, a “pacemaker” part of the hypothalamus that is highly sensitive to external stimuli, specifically light and darkness. Light signals it’s time to wake up and be alert, while dark means that it’s time to slow down and sleep.
While those signals are intensely tied to the sleep cycle, they have downstream effects on a host of biological functions. “I think of the circadian pacemaker as the conductor of an orchestra,” says Erin Flynn-Evans, who leads the NASA Ames Research Center Fatigue Countermeasures Laboratory. “It controls a whole concert of biological function. There are circadian clocks in the liver, in the gut, in reproductive hormones. The master pacemaker in the suprachiasmatic nucleus is sort of synchronizing the timing of all that biological function.”
But that internal timekeeper can’t always keep up with human behavior. When travelers move quickly across time zones, the circadian clock gets desynchronized from the exterior world, an experience most people know as jet lag. That mismatch can cause a range of symptoms including fatigue and bleariness, insomnia, and even digestive problems.
For most people, it’s a relatively rare event and just an inconvenience. But for workers like pilots and flight attendants, who may endure these changes daily, jet lag can affect their long-term health. Even relatively short hops affect cognitive function. One 2017 study published by researchers at Northwestern University found that professional baseball players who traveled over just two or three time zones for a game played worse. The same problems exist for shift workers like nurses, and people with irregular hours like long-haul truck drivers, who operate on schedules that keep them awake at night.
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“We know that having a persistent misalignment of our internal clock with the external clock that’s determining the timing of our activities comes with significant cost,” says Flynn-Evans.
Because the circadian system is tied into every bodily tissue, it is implicated in all kinds of diseases. If the clock is disrupted, research shows, cancer cells grow faster. Having an internal clock that’s perpetually out of sync with a person’s behavior can lead to increased risk for breast and prostate cancers.
Other research suggests that the clock facilitates the immune system, predicting when the body might encounter pathogens and coordinating a response, so a chronically unsynced clock might make people more susceptible to infections and cause constant, low-grade inflammation. It’s also been linked to heightened risk for cardiovascular problems and type 2 diabetes.
Jet lag is even an issue for astronauts, who may circumnavigate the globe every 90 minutes when in low orbit. Flynn-Evans says the body just can’t adapt to such a short day, so NASA has had to figure out interventions, like ensuring there are shades on all space vehicles’ windows. “It seems like a simple thing, but if you don’t plan for that you might not have that protection when you get into space,” she says.
The circadian clock problem could become trickier once future astronauts travel farther into space, like if NASA starts sending people to explore Mars, where a day is 39 minutes longer than one on Earth. That means astronauts will have to stay awake longer. “You can imagine that’s sort of like jet lag,” says Flynn-Evans. “You’re shifting your sleep later and later, and after just a few days, you’re going to be sleeping very much during what would be an Earth day and awake very much during an Earth night.”
Already, NASA teams on Earth that work with uncrewed Mars missions like the Phoenix lander and the Perseverance rover are adapting their sleep cycles to Martian time. A 2012 study in the journal Sleep by Flynn-Evans and her colleagues studying the Phoenix team found that most people could adapt to a longer day. But, she says, there are still a lot of open questions that can’t be resolved by studying people on Earth. For instance, blue light is an important wake-up signal to the circadian system, but it may be lacking on Mars, where the dust and a thinner atmosphere might affect the spectrum of light humans will encounter.
For the earthbound, scientists have been exploring drugs that might manipulate the clock. Last year, researchers at the National Institute of Biological Sciences in China and at UT Southwestern identified that a chemical found in mushrooms could reset the clock in human and mouse cells. Longdaysin, which has been tested in mice and larval zebrafish, kept one circadian protein from degrading, extending the animals’ clocks to be longer than a normal cycle. Nobiletin, which is found in citrus peels, amplified the highs and lows of the circadian cycle in human and rat cells, suggesting it might help synchronize downstream processes like metabolism, cardiovascular function, and immune response.
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But none of these chemicals have been tested in people yet. “That’s really the big step to take, to conduct a rigorous clinical trial type of study to evaluate its effect in humans,” says Jake Chen, whose lab at the University of Texas Health Science Center at Houston first described Nobiletin’s circadian effects in 2017. His lab and others are interested in whether it could help treat sleep disorders and reduce some circadian-related problems like neurodegenerative diseases and diabetes.
Chen says it takes time to run through all of the pre-clinical trials to show these compounds are safe before scientists start experiments involving people. And, because the ripple effects of tinkering with the internal clock could be wide-ranging, it’s hard to know what complications a drug could cause. “The circadian system is so complex—you manipulate protein in one way, the eventual outcome on the general circadian rhythm is a little bit unpredictable,” he says. So far, most studies have focused on how these compounds affect one specific protein in a cell. But that approach doesn’t show how changing that protein might affect hormone production in another organ, for example.
For now, Chen recommends that anyone who is trying to overcome jet lag stick to behavioral interventions. “Try to minimize your internal, intrinsic rhythm, which carries with it your previous location signature, and really align to your destination,” he says. That means staying awake during the local daytime—no midday naps or late-night adventures. He also sees promise in studies that show more general circadian regulation benefits from time-restricted eating, when people only eat during a short window and fast for more than 12 hours.
“The crazy thing with the best recommendations is they are pretty boring,” says Erin Flynn-Evans: Turn off screens and make the room dark when getting ready for bed. And in the morning, make sure there’s lots of sunshine to help your body wake up and stay alert. Sometimes hacking your system is as simple as adjusting the lights.
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