Don't stay up late! When you turn upside down day and night, skin and liver all know

Don't stay up late! When you turn upside down day and night, skin and liver all know

June 05, 2019 Source: Academic Jingwei

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People who spend the night have experience, even if there is a strong "will" support, the body clock will let us sleep in the middle of the night, we must sleep. Many studies have drawn evidence that people who are often reversed day and night will have disordered metabolism and endanger health.

In the latest issue of the top academic journal Cell, two papers back-to-back confirmed that the biological clock that senses diurnal changes in light and regulates metabolism and functions is actually spread throughout the body. In other words, when you stare at the computer screen or mobile phone late at night, even your liver and your skin can detect that you are upside down day and night. And these organs that are disrupted by rhythm may make the body more prone to health problems.

The "master clock" of the human body clock is located in the hypothalamus in the brain, sensing changes in day and night light within 24 hours, and regulating the physiology of the whole body. However, outside the central nervous system, scientists have also discovered in the past two decades that various organs in the periphery, such as skin and internal organs, also have clocks, and some genes in the cells will have fluctuations in expression levels within 24 hours.

But does the peripheral clock completely obey the master clock to achieve synchronization, or does it have independent functions? In order to find experimental evidence, scientists from the University of California, Irvine (UCI) and the Barcelona Institute of Biomedical Research in Spain formed a joint team to try to separate the biological clocks of the two organs.

The researchers first constructed a special class of mice that lacked an important gene, Bmal1. At the cellular level of the circadian clock, this is a key transcription factor that regulates the expression of many genes involved in circadian rhythms. Therefore, the various tissues of the whole body lack BMAL1 animals, the biological clock is completely shut down, and eating and sleeping are irregular, and accordingly they grow thin and weak, and premature aging.

On this basis, the scientists restored the expression of BMAL1 in the liver and skin, respectively. Then, mice with normal circadian clocks, mice lacking the circadian clock, and mice with a single organ recovery circadian clock were compared.

When these animals were in a standard 12-hour daylight, 12-hour dark night, the researchers tested their gene expression. Unexpectedly, in those mice with only the skin clock or the liver, despite the lack of the master clock, some of the genes in the corresponding tissue cells can change as the light changes as the normal state, just the degree of undulation. Has weakened.

Moreover, the analysis of metabolites shows that under the independent operation of the liver clock, the liver will perform some of its key metabolic functions autonomously. For example, metabolism of carbohydrates and amino acids, glycogen conversion. Nearly one-fifth of the 200 metabolites that have rhythm changes in the liver of normal mice are also retained in mice with only the liver clock.

From the mice that retained the circadian clock on the skin, the researchers observed that the cell renewal of the epidermis was retained by the circadian clock, and the phenomenon of premature aging of the skin slowed down.

However, when the researchers left the mice in a dark environment for 24 hours, the skin clocks of the skin and liver stopped working as the light changes. That is to say, the skin clock and the liver's biological clock can detect changes in light for some mechanism that is not yet clear!

“The results surprised us!” said one of the co-authors, Professor Sassone-Corsi of UCI. “No one thought that the liver and skin could be directly regulated by light.”

With this set of mouse models, the next international team also plans to gradually explore the circadian clocks of other organs and observe how different organs communicate, "how to break the metabolic pathways to control circadian rhythms, aging processes and overall health."

Many studies on circadian rhythms in the past have shown that sleep deprivation, diet, exercise and other factors will adjust the body clock. “Modern lifestyles can easily upset people's normal circadian rhythms, causing depression, allergies, premature aging, cancer and other health problems.” Professor Sassone-Corsi finally added, “Further mouse experiments may help us find people in the body clock” Not so dysfunctional 'the way.'

We look forward to the early release of remedies and improvements to help people who have been disrupted by the circadian rhythm – such as those who travel across time zones and work night shifts. But before that, we can still try to maintain good living habits every day. For example, don't let the screen light of the computer and mobile phone interfere with our biological clock before going to bed.

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