Eyes Wide Open

Eyes Wide Open

Sleep is fundamental to human physiology. So, why don’t we know more about it? And why are most of us not getting enough?

By Lauren Arcuri

No matter our differences, no matter where we are in the world, there’s something we all have in common: sleep. 

This physiological behavior is fundamental to human well-being. However, it still holds so many mysteries that science has yet to fully uncover. We still don’t know the answers to these questions: Why do we have different stages of sleep? What functions do these stages perform? How is sleep restorative to the body?

We do know how important sleep is. “In order to have normal physiology, normal cognition and normal emotions, we require sleep,” says sleep and anesthesia researcher Ralph Lydic, PhD, professor at the University of Tennessee, Knoxville.

The physiology of sleep is tightly tied to our circadian rhythm—a natural, 24-hour cycle that plays a role in when we are awake and asleep. It’s a carefully orchestrated symphony of our hormones and genetics, primarily influenced by light. As humans, our circadian rhythm is diurnal, meaning we are generally active during the day and asleep at night.

We need a consistent amount of high-quality sleep that occurs at night in sync with our circadian rhythm. However, for many of us, sleep quality is poor or happens at the “wrong” time. More than one-third of adults in the U.S. get less than seven hours of sleep a night, the minimum recommended by the American Academy of Sleep Medicine. More than two-thirds of U.S. high school students report getting less than eight hours of sleep on school nights, according to the Centers for Disease Control and Prevention. Further, 1 out of 5 people work what is considered “non-standard” hours, which typically requires sleep at the “wrong” time of day. 

Sleep and Human Health

The consequences of this chronic sleep deprivation may be profound. “We know sleep deprivation does terrible things to our physiology,” Lydic says. “Four nights of five hours of sleep or less, which is very common in medical residency training, very common if you’re a first responder, a young parent—very common for many of us—causes cognitive dysfunction that is equivalent to a blood alcohol level of 0.06. So it really, really matters.” 

Human sleep is characterized by a sleep cycle made up of four distinct phases or stages. In one night, a person typically goes through four to six total sleep cycles. The cycle begins with stage 1, basically “dozing off,” which usually lasts only one to five minutes. As the person falls asleep, they enter stage 2: their body temperature drops, their muscles relax, their brain activity diminishes and their breathing and heart rate slow. This stage can last 10 to 60 minutes.

Stage 3 sleep, which usually lasts 20 to 40 minutes per cycle, is also known as deep or slow wave sleep. During this time, thought to be important for repair and restoration, the brain’s activity is characterized by a type of brain wave called delta waves. As we emerge from deep sleep, we enter stage 4 or rapid eye movement (REM) sleep, when brain activity picks up and the body’s muscles (except eyes and breathing muscles) experience sleep paralysis. This is the phase of sleep when we dream, and it typically lasts 10 to 60 minutes per cycle.

A lot of people view sleep as a waste of time. We believe things like sleeping a lot is a sign of weakness. It shouldn’t be seen that way. Some people do need to sleep more than others, and that’s just your body.

Jason Carter, PhD

Lisa Marshall, PhD, professor at University of Lubeck in Germany, studies memory consolidation during sleep. She points out that people who are chronically sleep-deprived are usually unaware of the detrimental effects of it on things such as their reaction time, which could result in dangerous situations such as driving while sleep-deprived.

Marshall’s lab is learning that it’s not just one phase of sleep, such as slow wave or REM, that is important to memory consolidation but the interaction of those two sleep phases that seems to facilitate the process. What’s clear already is that sleep is deeply involved in memory formation, she says.

Research has shown that if we don’t get enough sleep, or we get sleep that is out of sync with our circadian rhythm, the consequences are significant for our mental and physical health. People who are out of sync with their body clocks are more likely to feel depressed, anxious or fatigued, according to a June 2021 study in Molecular Psychiatry. Studies have also shown that people who chronically sleep less than seven hours are at an increased risk for diabetes, obesity and cardiovascular disease.

“We’ve known for a little while, about a decade or two, that sleep is important, not just for the brain, which historically was the perception, but also really important for whole body health,” says Josiane Broussard, PhD, assistant professor at Colorado State University. Broussard’s research focuses on how sleep and circadian disruption affect metabolism. Some of her latest work studies the impact of insufficient sleep on insulin sensitivity. Previous research showed that insufficient sleep impairs insulin sensitivity at the whole body level. Broussard and her colleagues followed that process down to the cellular level, finding a reduction in insulin signaling in the fat cell itself.

Follow-up research suggests that based on the upregulation of genes involved in fatty acid processing and downregulation of genes involved in glycolysis, “a fuel switch might happen with sleep and circadian disruption,” Broussard says. “Basically, the muscle could upregulate its use of fat for fuel when people are sleep restricted.” That fits with previous research her team has done, which found that adipose tissue is less sensitive to insulin when someone is sleep-deprived and that both sleep and circadian disruption result in increased free fatty acids in circulation.

It’s generally accepted knowledge that sleep loss leads to higher levels of the “hunger hormone” ghrelin in the blood, Broussard says. “You’re likely to eat more food, and you’re more likely to crave higher reward foods like sweets and treats.”

While lack of sleep clearly affects metabolism, the effects of sleep and circadian disruption are widespread across body systems. “There’s hardly a hormone that’s not impacted,” she says. “It’s quite striking, actually.”

Artificial lights via screens and work hours that don’t respect circadian rhythms are causing us to lose sleep. We’re also fighting an uphill battle as aging itself affects our sleep. As we grow older, our circadian rhythm becomes less pronounced. That’s why older adults sleep more poorly.

“We have this 24-hour rhythm [that] our body does, a cycle that has a large positive and negative amplitude to it,” Marshall says. “This amplitude is somehow decreased as we age so that it’s more difficult to sync your sleep behavior to your current physiological rhythm.” 

What’s more, as people age, they get less of what we call deep sleep or slow wave sleep. Jason Carter, PhD, a professor and vice president for research, economic development and graduate education at Montana State University, says, “Slow wave sleep slowly decays as we age. And yet, it’s such an important stage of sleep. We’ve now seen how even our brain gets flushed out when we’re in deep sleep and might help prevent or delay things like Alzheimer’s disease.” 

We Americans are wonderfully pragmatic, but to a fault. We justify everything by saying, ‘well, it helps us do better work.’ But what about quality of life? And what about our health? What about all the other things that make us human?

Ralph Lydic, PhD

Although researchers have found the connections between lack of quality sleep and poor health, they have not yet been able to find medications that help us achieve “normal” sleep architecture, including the important slow wave or deep sleep. A May 2021 study in the British Medical Journal found that prescription medications for sleep disturbances did not help midlife women sleep better over a two-year follow-up period. “Sleeping pills are a suboptimal solution,” Marshall says. “Not only is deep sleep not facilitated, but most of the time they don’t induce REM sleep, either—only light, non-REM sleep.”

Enter the Pandemic

The coronavirus pandemic that began in early 2020 changed many people’s sleep habits and patterns—for better and for worse, scientists have found. Carter and his colleagues published research in October 2020 in Biology of Sex Differences analyzing the impact of state-mandated lockdowns on anxiety and sleep quality and comparing the differences between women and men. The lockdowns led to increased anxiety and reduced sleep quality for men and women, but the effect was more pronounced for women with respect to anxiety.

A number of studies quantified the impact of the pandemic on sleep. One out of Washington State University and published in April 2021 in Frontiers in Neuroscience looked at twins during the pandemic. One-third of subjects slept less, while another third slept more—but any change, whether more or less sleep, was associated with changes in self-reported mental health status. A meta-analysis in the Journal of Clinical Sleep Medicine in February 2021 found that 40% of people reported sleep problems during the pandemic and people with active COVID-19 had higher rates of sleep problems. In another study in Lancet Psychiatry in May 2021, as many as one-third of COVID-19 survivors reported insomnia. 

While several studies found that adolescents slept more during the pandemic, often due to remote learning start times being more flexible, a study in PLOS One in April 2021 found that remote learning actually led to less sleep, as students had less exposure to sunlight and their circadian rhythms became delayed. 

Will the changes that have been beneficial, such as later or more flexible work and school start times, survive as we shift to a “new normal” and return to in-person school and work? “It will be interesting if people end up getting better sleep because so many more people are working from home and have less of a time requirement to get up and commute. That would be my hope,” Broussard says. “That would be a really positive outcome. Now that people are given a little more freedom to live by their natural biological clocks, rather than by an imposed work clock, keeping some of that might make sense.” 

“It will be interesting to see how people respond,” Carter says. “Will the individuals that were able to consolidate and prioritize sleep a little bit more continue with that in a post-pandemic world? I hope they will. But I think the anxieties of COVID-19 really had more of a detrimental impact on sleep than the positive.”

How to Improve Sleep

Since it’s clear many of us are sleeping less than optimally—whether that’s too few hours, inconsistent sleep, circadian disruptions like early or swing shifts, or lack of deep sleep—what can we do to improve our sleep? Right now, most of what we know is that our sleep habits contribute to our sleep quality: timing, consistency and making sure we sleep seven to eight hours every night. But changing those things isn’t always a simple matter.

“The joke is ‘just sleep more,’” Broussard says. “Talk to any middle-aged woman who’s starting to have sleep issues, or people whose jobs keep them awake overnight, or people with babies and young kids—obviously, there are times when you just can’t get enough sleep, or you can’t sleep at the right time.” It’s also important to recognize that some factors, such as shift work, tend to disproportionately affect people in lower socioeconomic classes and historically marginalized communities.

These less-than-ideal sleep behaviors are unavoidable at times. Broussard’s lab is aiming to answer the question what can we do to reduce the risk that we know exists for increased diseases with sleep and circadian disruption? 

“We’re looking at whether you can ‘pay back’ a sleep debt by extending your sleep—to see if it improves metabolic homeostasis,” she says. Another study looks at whether someone who’s sleep restricted can offset some of those negative effects with exercise. Yet another is delving into whether manipulating food timing in relationship to circadian rhythms helps mitigate the effects of shift work. “We’re asking if moving food intake outside of the nighttime period, without reducing food amount, might reduce some of the health risk” associated with shift work, Broussard says.

Carter sees these questions as the ones at the heart of the field of sleep research moving forward. “I think that a big question is how do we leverage technology? We know how bad technology, like smartphones, has been for sleep,” he says. “But how can we leverage technology to actually help us with sleep?” Wearables and trackables are beginning to get better and better at monitoring our sleep, helping us track the impact of changes to our sleep routines and habits in both quality and quantity.

It’s also important for society to recognize that sleep is just as important a part of health as regular physical activity and good nutrition, Carter says. “Sleep is the third pillar of health, and it’s cost-effective to improve it, and we don’t emphasize that enough. I think there’s an unprecedented opportunity to take advantage of behavioral modifications that don’t cost a lot of money that can have huge impacts.”

Culture is also at play. “A lot of people view sleep as a waste of time,” Carter explains. “We believe things like sleeping a lot is a sign of weakness. It shouldn’t be seen that way. Some people do need to sleep more than others, and that’s just your body. We need people to feel comfortable with getting the amount of sleep that’s right for them.” While that’s seven or eight hours for most of us, a few people can do fine on five or six hours, while others need nine, 10 or even 11 hours to function optimally.

“We Americans are wonderfully pragmatic, but to a fault,” Lydic says. “We justify everything by saying, ‘well, it helps us do better work.’ But what about quality of life? And what about our health? What about all the other things that make us human?”

One strength that sleep research has, Lydic says, is its multidisciplinary nature. Sleep cuts across all disciplines because it affects everything about us, our entire physiology and all our systems. “I think many people are excited about computational biology combined with physiology,” he says. “I think this is going to allow people to make really big advances. Many of us grew up looking at XY, two-dimensional relationships. And now we have the computational power to look at many, many interacting relationships.”

With this power we may finally have the tools to untangle the remaining mysteries of the complex, multi-system phenomenon of sleep.  

This article was originally published in the September 2021 issue of The Physiologist Magazine.