Northwestern Magazine: The Rhythm of Sleep

It’s so slight, you don’t even feel it coming. You might feel a bit fuzzy, weightless, buoyant. It’s subtle — in the initial stages, your heart rate dips and your muscles relax. Before your brain waves become even slower, your body temperature falls. Finally, brain activity speeds back up, but your limbs are temporarily paralyzed and your eyes begin to dart behind your eyelids. Over the next several hours, this cycle will repeat at relatively regular intervals.

Until your alarm blares from your nightstand.

We may regard sleep as a period of pure rest and rejuvenation, but it’s so much more. And while we often hear that we need seven to nine hours a night, there’s more to that story as well.

Kristen Knutson

“Sleep health is multidimensional,” says Kristen Knutson, associate professor of neurology and preventive medicine at Northwestern’s Feinberg School of Medicine. “It’s sleep duration — are you getting enough sleep? But it’s also quality. It can also be timing. You could be getting what you think is a decent quality of sleep, and you might think that you’re getting enough sleep, but you don’t feel rested at the beginning of the day.”

The effects of insufficient or poor-quality sleep go far deeper than our energy level the next morning. As Northwestern researchers have shown, sleep is a key component of our cardiovascular, metabolic and cognitive health. In short, improving sleep can help us live longer, healthier lives.

THE MECHANISMS OF SLUMBER

If you’ve been up since 7 am, you might notice that with each passing hour after dinnertime, you feel more tired and ready for sleep. By midnight, you’re likely dreaming — or hoping to be doing so soon. This natural drive to sleep is known as sleep homeostasis, and it is one of the key mechanisms controlling sleep.

“Sleep homeostasis is a fancy word for something very simple: The longer you’ve been awake, the easier it is to fall asleep,” Knutson says.

Sleep is also controlled by the circadian clock, a 24-hour pattern naturally synchronized to the cycle of daylight and darkness. You can think of the circadian clock as your internal timekeeper, which, ideally, aligns with the time of day or night — so-called external time. That grogginess you experience after pulling an all-nighter or the jet lag you feel after flying from Rome to Chicago is due in part to your circadian clock being out of sync with external time.

The central circadian clock is in the hypothalamus region of the brain. Our pattern of sleep and wakefulness — the sleep-wake cycle — is one output, or rhythm, of our circadian system. (Our pattern of hunger and fullness, the so-called feed-fast cycle, is another.)

In recent decades, researchers at Northwestern and elsewhere identified that there are also circadian clocks in the pancreas, the liver and many other tissues. Controlling specific functions like insulin secretion, DNA repair and even stress response, these peripheral clocks are like musicians in an orchestra. The central circadian clock in the brain is the conductor, giving cues to the clocks throughout the body to stay in sync as much as possible. The “conductor” clock can fall out of sync, as we experience when we fly across time zones, and so too can the peripheral “instrument” clocks.

Northwestern Magazine: The Rhythm Of Sleep

Fred Turek

“Circadian biology refers to the 24-hour regulation of every physiological process in our bodies, and the sleep-wake cycle is just one of them,” says Fred Turek, the Charles and Emma Morrison Professor of Neurobiology at Northwestern’s Weinberg College of Arts and Sciences. When clocks are misaligned, so-called circadian disruption can lead to negative health outcomes. At the same time, insufficient sleep and poor-quality sleep are risk factors for a whole host of ailments from hypertension to .

More than half the genes at the heart of the central circadian clock were identified by Northwestern’s Center for Sleep and Circadian Biology (CSCB), which Turek directs. Martha Hotz Vitaterna ’92 PhD, a neurobiology research professor at Weinberg and CSCB deputy director, discovered a mutation in a mouse that helped identify the first molecular piece of the clock in mammals: the so-called Clock gene.

Northwestern Magazine: The Rhythm Of Sleep

Martha Vitaterna

“Twenty-five years ago, these were really two separate fields,” Vitaterna says of circadian biology and sleep science. While she acknowledges that some sleep issues may not be circadian-driven, “it almost becomes a chicken-and-egg question because, especially with humans, it’s very, very hard to mess with circadian rhythms and not mess with sleep. And conversely, it’s very hard to mess with sleep without messing with circadian rhythms.”

In the early 1990s, Turek recognized that understanding the role of circadian biology in the sleep-wake cycle could help researchers shed on the role of the circadian system in health and medicine more broadly. He set up a rodent sleep laboratory at Northwestern, and within a few years he and his team had earned millions of dollars in research funding.

“I would argue that Northwestern University has played a major role in integrating the two fields into what is almost one field today,” says Turek.

Fred Turek and Kristen Knutson discuss their long-standing professional relationship and the ways their different perspectives have improved each other’s research efforts on sleep and circadian timing, with the goal of improving human health and addressing health disparities.

In a 2005 study, Turek worked with Joseph Bass, the Charles F. Kettering Professor of Medicine at Feinberg, and his team to discover that when an animal’s clock gene is abnormal, the animal is more likely to become obese than an animal with a normal Clock gene eating the same food. “That told us there was some connection between the genes controlling the sleep-wake cycle and the circadian clock and obesity,” Bass says.

They also found that disrupting circadian rhythms was connected to the development of a metabolic syndrome consisting of symptoms related to cholesterol and glucose levels and fat accumulation in the liver and abdomen.

“So is it circadian disruption or sleep loss contributing to health problems?” Turek asks. “The answer right now is both.”
Northwestern Magazine: The Rhythm Of Sleep

AT THE HEART OF IT

If you’re walking in the woods and come upon a bear, your body’s autonomic nervous system — your fight-or-flight response mechanism — kicks into high gear.

Northwestern Magazine: The Rhythm Of Sleep

Mercedes Carnethon

“This is evolutionary. I want my autonomic nervous system to respond in a way that, if this bear slashes me, I don’t bleed out. I want my heart rate to go up so that I can prepare to run,” says Mercedes Carnethon, the Mary Harris Thompson Professor of Preventive Medicine and vice chair of that department at Feinberg. “Not sleeping well is a stressful situation, and when you’re under a lot of stress, your body is preparing for a fight by raising your blood pressure, raising your heart rate, making your blood more likely to clot.”

And when blood pressure stays high as a result of prolonged stress, Carnethon explains, the lining of the blood vessels suffers abrasions, triggering an inflammatory response that narrows the arteries and can lead to heart attacks and strokes.

“There’s a lot of experimental work that has shown that even a week of sleeping only four or five hours a night changes your autonomic nervous system,” Knutson says.

In a national four-site research project called Coronary Artery Risk Development in Young Adults (CARDIA), Knutson and Carnethon linked short sleep and poor-quality sleep to higher blood pressure and a greater increase in blood pressure over five years among non-Hispanic Blacks and white adults. Being a short sleeper was associated with a buildup of calcium in the coronary arteries and, in men, a thickening of some arteries. All of these, Knutson says, are risk factors for cardiovascular disease.

Carnethon acknowledges, though, that sleep and stress have a bidirectional relationship. “Nonrestful sleep is both a cause of stress and a consequence of stress,” she says. “It’s a total feedback loop.”

So too is the connection between poor sleep and our behaviors in response to our stress and our sleep loss: moving less throughout the day, eating less nutritious food, increasing caffeine intake — all of which may affect our risk for disease. “Short and poor-quality sleep can influence the risk of chronic diseases directly, through changes in pathways and mechanisms, and indirectly, through changes in the behaviors that you use to cope with nonrestful sleep,” Carnethon says.

In 2017 Carnethon found that sleep may explain some of the racial disparities in cardiovascular and metabolic diseases between African Americans and European Americans. Carnethon and Knutson are now studying the impact of sleep on racial disparities in blood pressure control among 2,200 young people across four cities: Birmingham, Ala.; Chicago; Minneapolis; and Oakland, Calif.

“Hypertension is the most commonly diagnosed medical condition in the country and the primary source of Black-white disparities in stroke, heart failure and chronic kidney diseases,” Carnethon says. “And we know that there are gaps in blood pressure control between Blacks and whites that aren’t explained by medication-use behaviors. We want to measure the extent to which the known differences in sleep are contributing.”

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