Stubborn genes: New research looks at how our bodies respond (or don’t) to night shift work

In nursing, there is a rite of passage that nearly everyone goes through — night shifts.

Sometimes, the shifts are clumped together, and sometimes, they are spaced apart, said Daniel Schweitzer, a nurse in Pittsburgh. But they always seem to have the same effect on his body clock.

“When you do a few nights, you get this permanent jet lag, where you’re never quite truly awake,” he said. “Your sleep schedule gets truly messed up.”

Researchers have been studying night workers for years, trying to better understand what happens to our circadian rhythms and our bodies when we are up-and-at-it at the time we’re supposed to be asleep. The findings are stark — night shift workers have a higher risk for diseases like obesity, diabetes, and cancer.

But what’s happening inside us? Have the genes that control our internal body clocks (there are trillions of clocks at work all at once, said one researcher who spoke to STAT) gone haywire, ramping up or tamping down in weird ways? Or are those genes digging in their heels, refusing to give up their cyclic nature, making it harder for the bodies of night workers to adapt to their flipped schedules?

It’s complicated, and might be a little bit of both, said Laura Kervezee, a postdoctoral fellow at McGill University who published a study in PNAS on Monday looking at, for the first time, how gene expression changes in a true night-shift-like environment. The findings do show a physiological disconnect — many of the genes associated with circadian cycles kept their rhythms, but seemed to fire at lower strength. Many genes couldn’t (or maybe wouldn’t?) adapt their expression to a flip-flopped sleep schedule. Gene expression related to metabolism, and the function of certain immune cells and potential cancer-causing signaling pathways were also altered.

“Very few genes adapt to this new night shift schedule,” Kervezee said.

Other studies have looked at gene expression in altered sleep schedules, but these results, she said, give us an introductory glimpse into bodies trying to manage a work schedule that affects about 25 percent of the population. Building on that glimpse, she said, could one day lead to interventions.

“It’s becoming more and more common because we expect services to be available 24/7,” she said, listing off professions with overnight shifts like health care, security, and warehouse work. “In the long term, it’s becoming clearer that there are negative health effects with it. We cannot stop night shift work because we want all these services as a society, but maybe we can devise strategies to help with night shift work.”

To do the current study, she and the team took eight volunteers, seven men and one woman, and put them through a night work simulation. The night before, she said, the volunteers slept according to their normal schedules, then the next night, started staying awake for four nights (the subjects didn’t sleep as long as they normally would have).

The McGill team took blood samples at intervals at the beginning and end of the simulation and looked at gene expression patterns in peripheral blood mononuclear cells, a subset of cells that are considered a good window into the general workings of the body. You can’t biopsy livers and such every few hours, she said.

“It’s a mirror for the rest of the body,” she said of the cells.

Beyond the dampened rhythm of circadian genes, there was also some perturbed expression in immune and cancer pathways, including the altered expression of genes related to natural killer cells, a first-line attack against tumor cells and infected cells. Kervezee said she would like to explore this finding more.

The study is small, she said. The volunteers were younger than the average shift worker. The abrupt night-sleep-to-night-work pattern was meant to emulate real shift work, where people might revert to normal patterns to spend time with family on days off. And the subjects were kept in dim light, so as not to confound the results since many oscillating genes are light-sensitive.

Despite those limitations, it’s a helpful study, said Frank Scheer, the director of the medical chronobiology program at Brigham and Women’s Hospital in Boston, who was not involved in the research.

“It’s a very nice study in that it simulates what shift workers go through,” he said.

The next step, said Kervezee, is doing the same experiments on real night shift workers. And after that, looking at interventions, whether behavorial, something that Scheer is interested in, or pharmacological, a potentially lucrative path.

There’s a name for the sleep side of the problem — shift work sleep disorder — and many sleep centers offer help to people who work odd shifts. There are also some precedents for drugs to be approved addressing the sleep side of circadian disruption.

But sleep is only part of the equation, said Scheer, and it’s a harder part to treat. His lab’s work has found changes in glucose tolerance, diet-related hormones, and increases in blood pressure and markers of inflammation.

“We’re looking at adjusting meal timing for this reason,” he said, based on animal and human studies.

Schweitzer, the nurse, said he thinks about meals as he works night shifts now. Knowing that how and when he eats might make a difference in gaining too much weight intrigues him.

He’s less interested in small molecules that might make him more of a night owl, unless his doctor was on board.

“I don’t know,” he said, now that he’s trying to work fewer nights. “I’ll just cope with the changes to my circadian rhythms rather than take a pill.”