The genetics behind short sleepers

September 3, 2019
Written by: Sarah Reitz

 

As many busy students and professionals will tell you, there just aren’t enough hours in the day to tackle their workload and also get the recommended 7-9 hours of sleep. Unfortunately, sleep time is commonly sacrificed in order to study more, meet deadlines, or get ahead in a career. So common, in fact, that nearly a third of U.S. adults get 6 hours of sleep or less each night. While you may feel that you function completely normally on reduced sleep, this is rarely the case. Studies have shown that people who experience short sleep perform significantly worse on cognitive tasks compared to when they are fully rested, despite reporting feeling mentally alert and focused1,2. Incredibly, however, a small subset of people do not seem to be affected by these shorter sleep durations, and now scientists are unraveling what sets them apart from the rest of us.

These natural short sleepers, estimated to make up less than 1% of the U.S. population, sleep for just 4-6 hours every night, yet feel fully rested. They do not have to train themselves to wake up early, or set alarms each night like many people currently running on reduced sleep. As their name suggests, natural short sleepers wake up naturally after 4-6 hours of sleep. When a non-short sleeper sleeps less than 7 hours a night, they suffer from cognitive impairment and are at an increased risk for many adverse health effects. However, natural short sleepers don’t appear to experience any of the physical or cognitive effects of sleep deprivation. Additionally, they are more optimistic, don’t suffer from jetlag, have a higher pain threshold, and may even live longer than the average person3.

Ever since the existence of natural short sleepers was revealed, scientists have wanted to know what sets them apart from the rest of the population. However, studying the underlying cause of natural short sleep is no easy task. Due to the many sources of artificial stimulation in the modern world – think alarm clocks and caffeine – it is difficult for scientists to distinguish natural short sleepers from “unnatural” short sleepers. To help identify true natural short sleepers, as well as try to pin down a genetic cause for this phenomenon, researchers study families who have a history of short sleep. By genetically testing individuals in a family who share the short sleep trait and comparing them to family members with normal sleep, they can identify which genes are responsible and test these in further studies.

Studies such as these have identified mutations in 2 specific genes thus far that produce natural short sleep. The first, a mutation in a gene called DEC2, was discovered in 20094. People with this mutation slept an average of 6.25 hours per night, while people without the mutation slept for 8 hours. A follow up study in mice showed that normally DEC2 helps control levels of orexin in the brain, a neurotransmitter that helps promote wakefulness, so that orexin expression matches the body’s internal clock5. By helping pump the brakes on orexin production at night, DEC2 allows the natural sleep-promoting systems in the brain to take over and make you sleep throughout the appropriate time of night.

The specific mutation inherited by natural short sleepers impairs normal DEC2 function, weakening its control over orexin production and leading to higher levels of orexin than normal. This increased orexin then causes the individual to stay awake for longer, resulting in the short sleep behavior. However, this mutation is very rare, so researchers knew there had to be other genetic causes for natural short sleep.

Just last week, the same group who identified DEC2 published a study identifying another genetic mutation that results in short sleep with no adverse effects6. By studying a family with 3 generations of natural short sleepers who did not have the DEC2 mutation, they uncovered a mutation in a gene called ADRB1, which encodes beta 1 adrenergic receptors. These receptors are known to be involved in heart muscle contraction and heart rate, but their role in the brain and central nervous system is not fully understood. Like the DEC2 mutation short sleepers, people with the mutated ADRB1 slept 2 hours less than the average person.

Before understanding how the mutated ADRB1 produces short sleep, the researchers first had to determine how normal ADRB1 functions in the brain. They found that ADRB1 is highly expressed in the dorsal pons, an area known to be involved in sleep and wake regulation. When they activated this population of ADRB1-expressing neurons in mice that were asleep, the mice immediately woke up. Thus, they concluded that ADRB1-expressing neurons are wake-promoting.

In order to understand how the short sleep genetic mutation affects the function of these ADRB1-expressing neurons, the team of researchers generated cells and mice with the same mutation as the natural short sleeping families. Just like in humans, the mice with the mutated ADRB1 slept significantly less than normal mice. They found that not only did the mutant ADRB1 protein break down more quickly than normal, but that the wake-promoting neurons in the dorsal pons were more easily activated when they expressed this mutant form of the receptor compared to the regular form. This suggests that the short sleep times associated with this mutation are likely caused by increased activation of wake-promoting neurons in the dorsal pons. In other words, the ADRB1 mutation tips the balance between sleep and wake to produce a brain that is more likely to stay awake than asleep.

These studies show that an individual’s sleep need is dictated not by personal preference, but rather by an actual biological requirement. The mutations in DEC2 and ADRB1 explain some cases of natural short sleep, but there are still other families with inherited short sleep, as well as sporadic cases of natural short sleepers who do not have either of these mutations, indicating that still other genes are likely involved. Additionally, we still do not understand how natural short sleepers appear to suffer none of the negative consequences of short sleep. Given that insufficient sleep was recently declared a national health epidemic by the CDC, understanding the link between good sleep and good health is critical for helping millions of people lead healthier lives. By studying this extraordinary group of people, we can hopefully uncover what a good night’s sleep truly means at the biological level.

 

 

Image References:

Cover image by Free-Photos from Pixabay.com, https://pixabay.com/photos/sleep-bed-woman-bedroom-sleeping-1209288/

 

References:

  1. Chen CW, Yang CM, and Chen NH (2012) Objective versus subjective cognitive functioning in patients with obstructive sleep apnea. Open Sleep Journal 5, 33-42
  2. Rangtell FH et al. (2018) A single night of sleep loss impairs objective but not subjective working memory performance in a sex-dependent manner. Journal of Sleep Res 28(1). doi: 10.1111/jsr.12651
  3. NPR (2011). Eight is Too Much for “Short Sleepers”. [podcast] Weekend Edition Saturday. Available at: https://www.npr.org/2011/04/16/135450214/eight-is-too-much-for-short-sleepers [Accessed 1 Sep. 2019].
  4. He Y et al. (2009) The transcriptional repressor DEC2 regulates sleep length in mammals. Science 325(5942):866-870
  5. Hirano A, et al. (2018) DEC2 modulates orexin expression and regulates sleep. PNAS 115(13):3434-3439
  6. Shi G, et al. (2019) A rare mutation of b-adrenergic receptor affects sleep/wake behaviors. Neuron 103:1-12

 

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