Why do people die from not sleeping? The deadly killer is in the intestines

A study on fruit flies shows that staying up late not only damages the brain, but also the intestines. Fortunately, everything can be restored before death.

Author: Peng Zhiping and Chen Tianzhen

Recently, a 1998-year-old Pinduoduo employee died suddenly on his way home late at night, which once again triggered discussions about the 996 work model of Internet companies. Whether it is a corporate employee working around the clock or a student, many of us are in a state of long-term lack of sleep.

What’s even more frightening is that after a day of hard work, many young people will fall into the curse of staying up late in revenge, watching TV series, reading novels, playing games... as if they can earn free time as long as they don’t sleep. Little do they know that life, like the TV series in their hands, passes by at a speed of X1.5.

Many people know that lack of sleep can be fatal, but why is it so? It is very curious. However, a study published in the journal Cell in June 2020 seems to have given an answer:

Through the study of fruit flies, scientists at Harvard Medical School found that the fatal effect of sleep deprivation is not in the brain, but in the accumulation of a substance called "reactive oxygen" in the intestines. What's even more surprising is that if these substances are removed, such as by neutralizing them with antioxidants, fruit flies will be safe even if they don't sleep, and their lifespan is the same as their normal counterparts. - This inevitably makes people wonder, is there any hope for those of us who stay up late?

Deadly sleep deprivation

In fact, just like not eating can kill you, the effects of lack of sleep are more serious and immediate than you might think. Complete sleep deprivation in a short period of time can be fatal, and long-term lack of sleep can also accumulate "sleep debt", causing heart disease, high blood pressure, diabetes and other diseases.

Scientists discovered this through animal experiments a long time ago. The first experiment was quite cruel: in 1894, Russian biochemist Maria Manaseina made 10 dogs in the laboratory walk around for 5 consecutive days without sleep, and all of them died. However, it is difficult for scientists to judge whether these deaths were caused by sleep deprivation alone or by overwork. They tried to use more reasonable experiments to separate the various factors that affect sleep.

In the 1980s, Allan Rechtschaffen of the University of Chicago designed a more gentle experiment: several pairs of mice were placed in specially designed cages, and once the mice were about to fall asleep, they were woken up to reduce the interference of excessive stimulation. Over time, the mice gradually became coarse-haired, thin, and died one after another after about 15 days. The lifespan of a normal mouse is 2 to 3 years.

So what does sleep deprivation do to people? In 2003, researchers at the University of Pennsylvania gathered 48 healthy adult men and women as subjects for a 14-day sleep deprivation experiment. The complete sleep deprivation experiment required the subjects to stay awake for three consecutive nights; the others were divided into three groups, sleeping 4, 6, and 8 hours per night respectively. The results found that sleep debt will continue to accumulate:

If the sleep time is 6 hours or less, the brain will have the same cognitive deficits as two nights of no sleep. In other words, even a moderate restriction of sleep time can seriously damage people's mental state when they are awake. In addition, the subjects may be too sleepy to even realize that their performance is getting worse day by day.

Chronic sleep deprivation can lead to sleep debt, but you may not realize it. | From the Internet

It's not just the brain that's damaged, it's the gut as well

Although it is known that sleep deprivation is so deadly, scientists have long found it difficult to identify from animal autopsy results what fatal effects sleep deprivation has on the body.

Most studies focus on the effects on the brain. But experiments show that when animals die from sleep deprivation, changes occur not only in their nervous system, but also in the cardiovascular system, digestive system, immune system, metabolism and other parts of the body. Dragana Rogulja of Harvard Medical School is an expert in studying neurons that affect sleep regulation. She speculates that the mystery of sleep may not only be hidden in the brain.

The team led by Rogulja chose fruit flies as the research object because people know enough about the genes of fruit flies and can easily regulate genes. They used fruit flies with thermosensitive channels in artificially modified neurons. As long as they are in an environment above 28 degrees Celsius, these fruit flies will be too hot to fall asleep. From about 10 days, the fruit flies that can never fall asleep will die one after another.

Dissections of the flies revealed that their tissues were intact, with one exception: their intestines were teeming with reactive oxygen species. In microscopic photographs, the small intestines resembled a blue maze illuminated by fiery purple, indicating that the ominous molecules were gathering.
Harmful reactive oxygen species accumulate in the intestines of fruit flies. The brighter the color, the more reactive oxygen species there are. ｜5W Infographics for Quanta Magazine

Reactive oxygen species are not uncommon in living organisms, and processes such as respiration, metabolism, and immune defense all produce reactive oxygen species. But if antioxidant enzymes do not remove reactive oxygen species, things can become very dangerous, as they can damage DNA and cause cell damage. Because the oxygen atoms in reactive oxygen species that carry unpaired free electrons have strong chemical reactivity, they can take away electrons from DNA, proteins, and lipids, leading to oxidative damage.

Fortunately, the consequences of staying up late can be compensated

Thankfully, while sleep deprivation can have deadly effects, it can be prevented in time.
Further research found that if the exhausted fruit flies were allowed to sleep on the 10th day, they would gradually recover. However, if they were deprived of sleep again after 5 or 10 days, they would still not be spared from death. In other words, the damage accumulated in the initial sleep deprivation takes time to be gradually repaired - for fruit flies, this period is a full 15 days of normal sleep.
Interestingly, catching up on sleep isn’t the only way to repair damage: When the researchers tried using antioxidants to neutralize harmful reactive oxygen species, the fruit flies were able to survive without sleep and lived just as long as their normally functioning counterparts.

But it is worth noting that reactive oxygen species kill fruit flies, but they are not necessarily the culprit for harming mice or humans, after all, they are different species.

But a small study of sleep-deprived humans showed that the composition of their gut microbiota changed, establishing another link between sleep and the gut — and telling us that sleep is not just a function of the brain, but an experience that involves the entire body.
Catching up on sleep in time can reduce the damage to the body caused by lack of sleep. | From the Internet

The fruit fly study solved a small problem about sleep, and at the same time, it led us to imagine a broader future. Perhaps one day we can truly crack the mystery of sleep, and humans may be able to survive without sleep just like fruit flies, as long as they are injected with some chemicals.

But before that day comes, sleep is still very important to each of us. When the night comes, it is better to lie down in bed. If you have to stay up late, make up for it as soon as possible.

(Editor: Gao Peiwen)

References: [1]https://www.quantamagazine.org/why-sleep-deprivation-kills-20200604/[2] Vaccaro et al., Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut, Cell 2020), https://doi.org/10.1016/j.cell.2020.04.049[3] Hans PA Van Dongen , Greg Maislin, Janet M Mullington, David F Dinges. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep. 2003 Mar 15;26(2):117-26. doi: 10.1093/sleep/26.2.117. [4]Everson et al. Cell Injury and Repair Resulting from Sleep Loss and Sleep Recovery in Laboratory Rats. Sleep, Volume 37, Issue 12, 1 December 2014, Pages 1929–1940, https://doi.org/10.5665/sleep.4244

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