author: academic Jun, from the title figure: Vision China

Lying up late is a status quo in modern society. Due to the influence of a series of factors such as changes in modern lifestyles and increasing pressure of social competition, staying up late becomes a new normal for people.

However, we all know that staying up late will bring great harm to our body, for example, staying up late will cause immune dysfunction, rough skin, disorder of the circadian body clock, and also cause neurasthenia, Headaches, insomnia, and more seriously, long-term staying up late can also cause sudden death.

Why do staying up late cause death? Is there any good way to make up for the harm of lack of sleep?

On June 4th, the research team led by Professor Dragana Rogulja of Harvard Medical School published the heavy research results in the world’s top journal Cell. The researchers found that the reason why long-term staying up late will cause premature death is It is due to the accumulation of oxides in the intestine, and the researchers further confirmed through experiments that by actively removing the oxides in the intestines of animals, even if they stay up late for a long time, their life expectancy is no different from that of animals that maintain normal work and rest.

Professor Dragana Rogulja said, “Our research revealed for the first time the cause of premature death of animals due to insufficient sleep, which opens up new research avenues for us to understand the full consequences of insufficient sleep, and in the future will also offset The damage to the human body provides ideas.”

A core question about sleep

Sleep is the foundation of our human and animal life activities. Scientists have been studying sleep for a long time, trying to understand the mysteries of sleep, but there are still many secrets that cannot be solved.

Sleep is necessary for almost all animals known at present, if there is not enough sleep, it will cause a series ofserious consequence. In humans, the effects of sleep loss are manifested in chronic sleep disorders, heart disease, type 2 diabetes, cancer, obesity, depression and other diseases.

In addition, as early as 1983, a Chicago scholar found that long-term sleep deprivation will inevitably cause animal death through research on rats.

Later, scientists have been exploring for decades, but one of the core issues remains unresolved, which is why animals die if they don’t sleep.

The brain is not the key, but the intestine is

Although previous studies have proved that prolonged sleep suppression will inevitably lead to premature animal death, in order to find the mechanism behind the death caused by sleep deprivation, most researchers have focused on the brain. After all, the brain is the main organ that controls our sleep. However, based on the study of the brain, no researcher has found useful clues.

Dragana Rogulja, a professor of neurobiology from Harvard Medical School, has long been devoted to the study of sleep deprivation. In order to find the cause of death of animals without sleeping, they selected fruit flies as experimental subjects. Because the genes of Drosophila are very similar to humans, many sleep regulation genes are shared with humans; at the same time, the life cycle of Drosophila is short, which is also suitable for researchers to observe.

Since the fruit fly can fall asleep even during the vibration of the wings, the researchers passed the baseDue to the regulation of specific nerves in Drosophila, it expresses a heat-sensitive protein. When Drosophila is placed in an environment of 29 degrees Celsius, this protein can always keep neurons active, thereby inhibiting the sleep of Drosophila.

Subsequently, the researchers found that after 10 days of sleep deprivation, the mortality rate of fruit flies reached the peak, and after 20 days, all the sleep deprived fruit flies all died, but the control group of fruit flies maintained normal work and rest Can survive for 40 days. In other words, sleep deprivation does cause premature death of fruit flies.

So why do sleep-deprived fruit flies cause death? Since the death rate of fruit flies peaked around day 10, the researchers looked for the difference between sleep-deprived fruit flies and normal control fruit flies on that day and the previous days.

However, as with previous studies, no matter whether it is sleep deprived fruit flies or normal fruit flies, their brains and most other body tissues have not changed significantly. In other words, the brain is not the organ that causes the death of fruit flies.

Sleep-deprived fruit flies gradually increase intestinal ROS levels on days 1, 7, and 10 (above); sleep-recovered fruit flies on days 5, 10, and 10 15 days intestinal ROS level gradually decreased (below)

Finally, in the course of the research, the researchers still found an obvious difference between the two, that is, a large number of oxides accumulated in the intestines of sleep-deprived fruit flies, these oxides are highly reactive oxygen molecules, They will destroy a lot of DNA and other components in the cell.

At the same time, the researchers also confirmed that the accumulation of oxides is directly proportional to the mortality of Drosophila, also peaked around day 10, and after stopping sleep deprivation, the level of active oxides in the intestines of Drosophila also Will decrease.

Subsequently, the researchers repeated this experiment in mice, further proving that only active sleep-deprived animals accumulate active oxides in the intestine, which in turn induces animal death.

Neutralizing oxides can offset the harm of lack of sleep

Since animals with continuous sleep deprivation accumulate active oxides and induce premature animal death, can artificial removal or neutralization of these oxides prolong animal life?

For this reason, researchers have found dozens of antioxidants. These compounds can not only neutralize active oxides, but also can be used as food supplements, such as melatonin and NAD.

By supplementing these antioxidants with fruit flies, the researchers found that sleep-deprived fruit flies have normal or near-normal lifespan after using antioxidant supplements. At the same time, normal fruit flies supplement After these substances, there is no change in life. In other words, these antioxidants can prolong the lifespan of deprived fruit flies without any other effects.

At the same time, the researchers also used gene regulation to promote the expression of antioxidant enzymes in the intestinal tract or brain of Drosophila. It was found that overexpression of antioxidant enzymes in the intestine can effectively extend the lifespan of Drosophila, while the antioxidant enzymes in the brain are over Expression has no significant effect.

This further proves that the accumulation of active oxides in the intestine plays a central role in death from sleep deprivation. However, researchers have not been able to figure out why lack of sleep can lead to accumulation of active oxides in the intestine, and why it is so fatal.

Professor Dragana Rogulja said, “Many of us have long-term lack of sleep, even if we know that staying up late is harmful. We have now solved a core problem, that is, the lack of sleep damages the biological mechanism of human life, and this It was found that at least for fruit flies, it can be achieved without sleeping or death.”

Source:
https://doi.org/10.1016/j.cell.2020.04.049

https://www.eurekalert. org/pub_releases/2020-06/hms-sda060120.php


author: academic Jun