Don’t stay up late! One-third of human life is spent in bed?

Sleep is universal and essential to all organisms with a nervous system during evolution. The problem is that sleep makes us more vulnerable to predation. Why animals sleep despite the constant threat of predators and how sleep affects our brains remain a mystery.

Image source: www.pexels.com

We generally feel that sleep is an irresistible thing. Even if we get a longer awake time through drinks such as coffee, the sleepiness will become more and more serious. Therefore, sleep cannot be easily deprived through drugs, which also implies that sleep itself is necessary for survival.

In order to explain the necessity of sleep, many studies have given answers from different angles: sleep can maintain normal hormone secretion rhythm, reduce the risk of cardiovascular and cerebrovascular diseases, and even keep our skin moist and smooth. However, these reasons are not enough for creatures to sleep at the risk of being hunted, and the fundamental reason behind it is still confusing.

Previous studies have shown that sleep pressure builds up in our bodies while we are awake. This pressure increases the longer we stay awake, decreases during sleep, and is at its lowest after a good night's sleep.

What causes sleep pressure in the body to build up to the level where we feel we must sleep, and what happens during the night to reduce that pressure to the level where we are ready to start the day? In other words, what is the nature of sleep pressure?

Scientists have turned their attention to the core of life - DNA. But DNA is always in danger of breaking. When we study or work hard during the day, a large number of DNA breaks will occur. Some drugs such as oxaliplatin can also induce DNA breaks and cause cell death.

However, the DNA breaks induced by learning and work are not meaningless. Because DNA is so complex, in order to more efficiently express the required genes quickly, DNA will be broken at specific sites, so that the proteins required for learning and work can be synthesized quickly.

Image source: www.eurekalert.org

Research has found that the longer you work or study, and the longer you concentrate, the more DNA will break in a day. Although they ensure efficient operation, such a mechanism obviously has endless consequences. Broken DNA is like a time bomb that can cause cell death or cancer at any time.

A new study was recently published in the journal Molecular Cell. Israeli researchers discovered through studying the sleep mechanism of zebrafish that these broken DNAs will be repaired during sleep, thus taking a new step towards solving the mystery of sleep.

Image source: doi: 10.1016/j.molcel.2021.10.026.

The research team found that DNA damage in neurons continues to accumulate during wakefulness. When you are addicted to "996", the excessive DNA damage in the brain has reached a dangerous level that must be reduced.

To create more DNA breaks, the researchers induced DNA damage in zebrafish using radiation and other methods to examine how it affects sleep. Zebrafish are the best model organism to study this phenomenon because of their nocturnal sleep characteristics and simple brains similar to humans.

Image source: doi: 10.1016/j.molcel.2021.10.026.

The experiments showed that at some point the accumulation of DNA damage reaches a maximum threshold and sleep pressure increases to such an extent that the urge to sleep is triggered and the fish go into a sleep state. The subsequent sleep promotes DNA repair, thereby reducing DNA damage.

After confirming that accumulated DNA damage was a factor driving sleep, the researchers were eager to see if it was possible to determine the minimum amount of sleep zebrafish needed. They found that 6 hours of sleep per night was sufficient to reduce DNA damage. If they slept less than 6 hours, DNA damage was not reduced sufficiently and the zebrafish continued to sleep even during the day.

Next, the researchers needed to figure out what molecules in the brain tell us we need sleep to promote DNA repair? They found that the protein PARP1 is crucial.

Image source: doi: 10.1016/j.molcel.2021.10.026.

PARP1 is part of the DNA damage repair system and is one of the first proteins to respond. PARP1 marks sites of DNA damage in cells and recruits other molecules to repair DNA damage.

Through molecular biology experiments, the researchers found that increasing PARP1 not only promotes sleep, but also increases DNA repair during sleep. Conversely, reducing PARP1 makes zebrafish unaware of their need to sleep and no DNA damage repair occurs.

Further studies were conducted in mice using electroencephalography. As in zebrafish, inhibition of PARP1 activity reduced the duration and quality of non-REM sleep. This suggests that PARP1 is able to tell the brain that it needs sleep or it will be in danger.

Image source: doi: 10.1016/j.molcel.2021.10.026.

The corresponding author of the article said that the next task is to study the specific mechanism by which PARP1 senses the damage threshold. Their findings may be used to explain the potential connection between sleep disorders and neurodegenerative diseases.

And for us, it's another excuse to take a nap at work. Hard-working superstars, will you continue to work overtime tonight?

References:

[1] David Zada, et al. Parp1 promotes sleep, which enhances DNA repair in neurons. Mol Cell. 2021 Nov 12;S1097-2765(21)00933-3. doi: 10.1016/j.molcel.2021.10.026.