October 4, 2022

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Cell: The reason for staying up late to death has been found!

Cell: The reason for staying up late to death has been found!



Cell: The reason for staying up late to death has been found! The problem is not in the brain or heart, or in it!

When lying in bed and resting, even if your brain is awake, it can restore your energy. Whether you can sleep or cannot sleep, it is a victory. Moreover, reducing the stress of falling asleep can actually help you fall asleep faster.

Many of us are in a state of long-term lack of sleep. Even if we know that staying up every night is not good for the health of the body, we still do it…Understand the biological principles of sleep loss harming the body’s health so that we can prevent it. Loss of sleep damages the health of the body.

In a research report titled “Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut” published in the international journal Cell , researchers from Harvard Medical School found that insufficient sleep may pass through the intestines of the body. Reactive oxygen accumulates in the tract and causes death.

Cell: The reason for staying up late to death has been found!Image source: Alexandra Vaccaro, et al. Cell , 2020; doi:10.1016/j.cell.2020.04.049


ROS are induced hair factor for death

In the article, the researchers used fruit flies and mice to conduct research and found that sleep deprivation/deficiency can lead to the accumulation of reactive oxygen species (ROS , reactive oxygen species) and oxidative stress effects, especially in the intestine ; ROS is not only It is related to sleep loss, and it is also a driving factor in inducing death.

Neutralizing active oxygen can effectively prevent oxidative stress.   At the same time, it can also allow fruit flies with little or no sleep to have a normal life span.

Through oral antioxidants Or the transgenic expression of antioxidant enzymes that target the intestinal tract may rescue the damage caused by ROS.

Researchers believe that death caused by severe sleep deprivation may be caused by oxidative stress, and the intestine is at the center of this process.

When the accumulation of ROS in the body is blocked, if you do not sleep, Survival of the organism may be possible.

In this study, researchers revealed the cause of death caused by experimental sleep deprivation.

They said that the elimination of ROS may be a daily sleep function, but there is also a possibility that sleep loss produces a unique Adverse conditions lead to the accumulation of ROS. The production of ROS may be due to increased production, decreased clearance, or both.

The body’s long-term awakening state may directly affect the intestines, but the accumulation of ROS may also be derived from The result of signals from the nervous system or other tissues.


Most research focuses on the brain

Insufficient sleep can directly induce the generation of endoplasmic reticulum pressure in the intestines, which triggers oxidative stress in the tissues .

Previously, researchers have conducted studies on animal models and found that long-term lack of sleep can lead to premature death of individuals, in order to try to find sleep How deficiency induces body death, most of the relevant research focuses on brain research, because the brain is the source of sleep, but researchers have not yet come to some conclusive results.

The researchers found that fruit flies can fall asleep by physically shaking, so they genetically engineered fruit flies to express a heat-sensitive protein in specific neurons in the brain.

The activity of this protein can inhibit sleep. When fruit flies are placed in an environment of 29 degrees Celsius (84 degrees Fahrenheit), the protein induces neurons to remain active, thereby blocking the flies’ sleep.

After 10 days of temperature-induced sleep deprivation, the mortality of fruit flies increased sharply until all fruit flies died at 20 days.

Under the same environmental conditions, normal sleep control fruit flies could survive for about 40 days.

Since the mortality of fruit flies will increase around the 10th day, the researchers wanted to find markers that induce cell damage in their bodies.

They found that there is a significant accumulation of ROS in the intestines of fruit flies with lack of sleep.

A highly active oxygen-containing molecule, in most cases it will damage the function of DNA and other components in the cell, thereby inducing cell death. Researchers say that the accumulation of ROS will reach about 10 days after the lack of sleep in Drosophila.

At the peak, when the loss of insomnia is improved, the level of ROS in the intestine of fruit flies will decrease.

Other experimental results have shown that only those animals that have experienced sleep loss will accumulate ROS in the intestines , and the intestine is the main source of this lethal ROS .

Cell: The reason for staying up late to death has been found!Image source: Alexandra Vaccaro, et al. Cell , 2020; doi:10.1016/j.cell.2020.04.049

Researcher Vaccaro said that sleep deprived fruit flies die at the same rate every time. When we look at the markers of cell damage and death, the most significant tissue is the intestine.

In addition, the researchers also used gentle and continuous The mechanical stimulus to keep the mice awake for up to 5 days to analyze whether the accumulation of ROS also occurs in other species.

Compared with control animals, ROS levels in the small and large intestine tissues of mice with insufficient sleep increased , but not in other organs.

This finding is consistent with the results observed in Drosophila.

In order to clarify whether ROS in the intestine can play a causal role in death induced by sleep deprivation, the researchers analyzed whether inhibiting the accumulation of ROS would prolong the survival of animals.

They tested a variety of compounds that have antioxidant properties that can effectively neutralize ROS, and finally identified 11 compounds.

When given to fruit flies as a food supplement, they can make sleep deprived fruit flies have a normal or nearly normal lifespan; These compounds include melatonin, lipoic acid and NAD (nicotinamide adenine dinucleotide), which can effectively remove ROS from the intestine.

It is worth noting that the supplement does not seem to prolong sleep and does not deprive fruit flies. Life.

Researchers believe that the accumulation of ROS in the intestine may play a central role in inducing the premature death of sleep-deficient fruit flies.

At present, researchers still do not know why lack of sleep induces the accumulation of ROS in the body’s intestines, and why this It can have fatal effects; similarly, death may be due to intestinal damage or systemic effects produced by high levels of ROS.

During periods of sleep deprivation, the level of ROS in the body’s intestines will begin to rise.

This may be a protective response. Under natural conditions, animals may fall asleep before ROS reaches a dangerously high level.

This possibility may be Yes, lack of sleep can interfere with the body’s hunger signaling pathway, so the researchers also measured the food intake of fruit flies to analyze whether there is a special relationship between eating and the risk of death.

They found that some sleep-deprived flies eat more during the day compared to control flies without sleep deprivation.

However, restricting food intake seems to have no effect on the survival of flies, which may indicate that , Factors other than food intake may also be involved.

Researchers are currently conducting in-depth research to identify specific biochemical pathways that induce the accumulation of ROS in the body’s intestines and subsequent physiological interference.

The results of this article can also help researchers develop new therapies that can neutralize the negative health consequences of sleep loss.

References:

1.Alexandra Vaccaro, Yosef Kaplan Dor, Keishi Nambara, et al. Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut. Cell, 2020; doi:10.1016/j.cell.2020.04.049
2. Sleep, death and … the gut? https://www.sciencedaily.com/releases/2020/06/200604152053.htm

Cell: The reason for staying up late to death has been found!

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