SCIENCE

New Study Links Chronic Jet Lag To Weight Gain, Early Breast Cancer Onset

Disrupting the body's circadian rhythms may be even worse than previously believed.
Passengers sleep on a flight from London to Dinard, France.
Passengers sleep on a flight from London to Dinard, France.

Anyone who's flown across the country knows jet lag can be unpleasant. But a growing body of research suggests that subjecting yourself to jet lag on a regular basis can also have major consequences for your health: weight gain, impaired memory -- and, according to one new study, even a higher risk for cancer.

To produce this last finding, a team of researchers from the Netherlands raised female mice that were genetically predisposed to breast cancer in an environment that simulated chronic jet lag, in which the timing of light and dark, and warm and cool, were swapped once a week.

"Imagine that you were flying from Amsterdam to Australia one week, and then flying back the next week, for your entire life," said Harry van Steeg, a researcher at National Institute of Public Health in the Netherlands, and one of the authors of the study. "That's actually more or less the exposure we did."

They found that the mice living in this time-shifted environment developed breast cancer far more quickly than those in a control group, who were raised in a normal environment. The time-shifted mice developed tumors in an average of 42 weeks, while the control mice developed them in an average of 50 weeks. The jet-lagged mice also gained significantly more weight than the control group, even though they didn't eat any more food. 

Though the mechanisms behind these adverse health effects still aren't fully understood, Erasmus University professor Bert van der Hoorst, another co-author on the paper, said the most likely explanation was that they stemmed from problems in the mice's circadian system, the "internal clock" that can be found in virtually every organism on earth and that control bodily functions as crucial as breathing, digestion and sleep. 

The circadian system in mammals is made up of two basic parts: a central clock in the brain that takes timing cues from environmental inputs, especially light, and peripheral clocks in the rest of the body's organs that take cues from that central clock. When the environmental inputs to the brain change their timing -- as they do with jet lag -- it takes a while for the brain's circadian rhythm to catch up, and even longer for the peripheral clocks to adjust their mechanisms.

While these two systems are out of sync -- which for the mice in this study was their entire lives -- all sorts of health issues can arise.

"The general hypothesis is that certain processes in the body take place at a certain time of day. These processes may be incompatible with each other, so you need to separate them in time," said Harvard professor Frank Scheer, who studies circadian rhythms as the director of the Medical Chronobiology Program at Brigham and Women's Hospital but was unaffiliated with this paper. "If different organs in the body are out of sync with one another, they may end up performing functions that are incompatible."

Scheer said one of the interesting things about this new study is that it demonstrated a link between circadian cycle disruption and cancer even in the absence of several factors that are thought to be contributing factors. Mice don't produce melatonin, a sleep-related hormone that is thought to have cancer-fighting properties, and neither of these mice cohorts were exposed to sunlight, so they had the same levels of vitamin D, which some believe could play a role in cancer defense. 

Surprisingly, the mice in the jet-lagged cohort also didn't sleep less than the others; they actually may have slept more. (The researchers didn't directly measure sleep -- they used physical inactivity as a proxy for sleep -- so the sleep figures are approximate.) That suggests the timing of sleep may be as important as the duration of sleep, but it also highlights the difference between the sleep-wake cycle and the circadian cycle more generally. 

"A lot of people confuse the two," Scheer said. "But they're not the same. The sleep-wake cycle is just the most obvious impact of the circadian rhythm. You don't feel your cortisol levels changing or melatonin levels changing, or even your body temperature, unless you have a fever. But you do, of course, notice sleep."

All this lends credence to the idea that circadian cycle disruption in and of itself could be carcinogenic. 

These findings, like those of any medical study using an animal model, aren't necessarily indicative of what would happen in a humans -- though van der Hoorst said the structure of the organs involved in these effects were "highly identical in humans and mice." 

"Of course this needs to be proven and validated in human studies, but I would be very surprised if what we find in these mice would not be the same in humans," van der Hoorst said.                             

Moreover, these findings mirror those of epidemiological studies of humans whose jobs force them to disrupt their internal clock regularly, such as nurses who work the night shift, and flight attendants and pilots who staff intercontinental flights. They, too, are at higher risk for breast cancer and obesity. This link is so widely accepted that the World Health Organization classifies shift work as a "probable carcinogen."

"On the basis of epidemiological data, there was already an association between the two, but there was no causal evidence," said van der Hoorst. "This is the first real evidence that if. If you live out of phase with your circadian clock, then you are at risk for breast cancer and increased body weight."