A look at how ‘sleep genes’ may affect our circadian rhythms


Dr. Takahashi received the prestigious Peter C. Farrell Prize in Sleep Medicine from Harvard Medical School in November 2016. The award is given annually in recognition of outstanding research in sleep medicine.
Why we need sleep is an unsolved medical mystery. In the United States, 40 to 60 million people – around 15 to 20 percent of the population – have experienced sleep problems such as insomnia.

But a discovery my colleagues and I made in 2016 may hold the key to treating sleep disorders in the future. Our research suggests that sleep may be key in “resetting” our bodies to function properly the next day, and two specific genes may determine how much we sleep and how much we dream.

New discoveries about sleep and the body

We know people feel miserable when they don’t get enough sleep. But what does sleep actually do for our health? We typically think of sleep as a brain phenomenon rather than a function of the whole body.

Let’s start with the basics. Most of us feel periods of alertness and sleepiness throughout the course of a 24-hour day. This is known as our circadian rhythm, or internal clock, which changes slowly over the course of our lives. Data from the National Sleep Foundation indicate that the strongest sleep drives in adults occur from 2 to 4 a.m. and from 1 to 3 p.m.

When we go to bed for the night, we should experience four sleep cycles:

  • Stage 1: Between wakefulness and sleep
  • Stage 2: Mid-range sleep that accounts for around half of a normal sleep cycle
  • Stage 3: Deep sleep in which some dreaming may occur
  • Rapid eye movement (REM): Associated with vivid dreaming and the processing and storing of memories
A normal sleep pattern should include long stretches of non-REM sleep (stages 1 through 3) followed by short rounds of REM sleep.

In 2016, our team found that genetics play a major role in regulating sleep cycles in mice. We singled out one gene in mice that controls the amount of REM sleep needed and a second gene that controls the amount of non-REM sleep needed.

This is an important finding because we know little about the genetic underpinnings of sleep, and identifying genes that control sleep gives us a molecular entry point to understanding what causes it.

Forward genetics and theories about sleep

We made this discovery using a method called forward genetics. In forward genetics, we start at the functional level (sleep) and work our way back to the gene. This is somewhat opposite of the traditional research method, which starts with a gene and then asks what the gene does. Forward genetics is an unbiased approach to research. We aren’t looking at particular genes or candidates that we think might be involved. Rather, we randomly alter genes and observe whether those alterations cause changes in sleep.

In our experiments, we altered the genome sequences of lab mice and observed them for changes in their sleep patterns. It might seem like a long shot to randomly alter genes and look for clues, and in a way, it is. In a November 2016 NBC News interview, I compared the concept of forward genetics to playing the lottery, but the probability that we’ll find an interesting, relevant change in the lab is around one in 1,000 – much better odds than winning the Powerball!

Our next challenge will be to find out which genes – and how many – affect human sleep cycles. We may be able to answer the ultimate question: Does the human body need to sleep, or is sleep vital for our brains only? If we can pinpoint the specific genes in humans that control our sleep cycles, we may in the future be able to treat sleep disorders by developing drugs that act on these gene targets.

There’s ample evidence to suggest that sleep is a brain recovery process. We know that many functions occur while we sleep, including processing and storing the previous day’s memories.

Changes in connections in our brains also occur during sleep. Some researchers theorize that while we’re awake, brain connections involved in learning are strengthened. But this can’t go on continuously, so our brains “scale down” these connections while we sleep in order to reset and begin the process the next day.

Another idea is that the brain is “cleansed” at night. Each of us has a system of cerebral fluid flowing through our brains, and research suggests that this process is more active during sleep. There’s fascinating research to suggest that toxic chemicals such as the amyloid precursor protein (APP), which has been linked to the development of Alzheimer’s disease, might be cleared more efficiently during sleep as well in experimentsperformed by Maiken Nedergaard, M.D., S.M.Sc.

Ample evidence suggests sleep is a brain recovery process. If you’re having persistent sleep problems, seeing a doctor can help.

Barriers to getting enough sleep

The development of our modern, 24/7 society has shifted our sleep cycles. Whereas historically men and women in the main went to bed at sundown and woke at sunrise, we now flood our homes and offices with artificial light and stay up late until our work is complete. 

Compounding this issue is a boom in shift work. As many as 20 percent of adults work second shift late into the evening or third shift overnight. Altering your natural sleep schedule by even six or eight hours can seriously affect your sleep cycles if you don’t effectively block out sunlight and day-to-day noise when the rest of the world is awake.

Even young kids and teens today face shifted sleep cycles. School starts early in the morning, and kids may have to wake up before sunrise to catch the bus or get to before-school care so their parents can go to work. Young kids need a minimum of eight to 10 hours of sleep each night. Teens have a naturally delayed biological clock – they tend to be night owls and sleep later in the morning. 

Late nights and early mornings can lead to lack of concentration, moodiness, fatigue, and other effects of sleep deprivation in kids and teens. Chronic sleep deprivation also has been linked with high blood pressure, obesity, and other serious health concerns in adults.

How to get a good night’s sleep

Kids need a consistent bedtime routine, and it’s also important for adults. These are two of the main recommendations we give patients who have trouble sleeping:

  • Avoid electronics at bedtime: Light inhibits the production of melatonin, a hormone that naturally increases at night and promotes sleep. Controlled experiments show that reading on a tablet can delay sleep up to an hour when compared to reading a regular book.
  • Maintain a regular schedule: As often as you can, go to bed and wake up on a consistent schedule every day, even on the weekends. Doing so will give you a better chance at a full night’s sleep.
If you have persistent sleep problems, it’s important to visit with your doctor. You may be suffering from a sleep disorder that requires treatment.

The more we learn about sleep and genetics, the better we’ll be able to understand why we need it and how to treat sleep disorders more effectively. Though there are many unknowns about sleep, there’s one thing we know for certain: It’s vital to our health. Getting adequate sleep needs to be a priority in our busy schedules.

Discover expert tips to get the sleep you need with this 2016 blog article by Amrutha Pavle, M.D., and learn more by visiting the National Sleep Foundation website.