This article is from WeChat official account:Gezhilundao Forum (ID: SELFtalks) , author: Zhang Hongjun (neuroscience researcher at the Institute of Chinese Academy of sciences), the original title: “” early Bird “and” night owl “sleep clock, may be caused by genetic | Zhang Hongjun “, the title picture comes from: unsplash
Sleep is a topic of great concern to everyone, so how many people wake up by the alarm clock every day? A person who wakes up on an alarm clock is not a good sleeper.
There is a gold standard, relying on the normal cycle of the biological clock to wake up oneself is considered a good state of sleep.
What is the biological clock?
Because the earth circulates day and night 24 hours a day, people have the so-called life form of working at sunrise and resting at sunset.
In fact, there are many very important topics related to life sciences, such as hormone metabolism, which is to study the difference in human endocrine within 24 hours a day.
There are also studies on eating awake. They study the metabolism in the body, such as how nutrients are accumulated and how fat is produced.
There is also a very important research on the molecular clock. The molecular clock represents the existence of a time timer in every cell to maintain the operation of the entire life axis .
There have been many discoveries in the study of biological clocks in the ancient century, including China’s “Yellow Emperor’s Internal Classic”, and the observation of day and night in ancient Egypt and the Western world.
The biological clock experiment in the 18th century
Here is a key experiment done by French Mailan.
Everyone knows that the leaves of mimosa are open during the day, and the leaves will close at night.
Few people pay attention to the details and study whether the cycle that mimosa goes through 24 hours a day is triggered by light.
So Mai Lan designed a box, the box is opaque, he put thePut the mimosa in, It turns out that the mimosa leaves open during the day when there is no light.
This proves that living organisms have a relatively stable, 24-hour menstrual cycle.
In the 1970s, gene mutation screening became a very important genetic research method. Two scientists, Konopka and Benzer, decided to use genetic screening to study the biological clock.
They are very clever, starting with changing the emergence cycle of fruit flies, that is, the process from pupae to adults.
Drosophila emergence cycle record
The picture above is the daily emergence record of normal fruit flies, which was completed in the morning.
They collected many mutant fruit fly strains and found that the emergence time of one strain of fruit flies was very messy.
There are adults appearing at any time of the day, which means that its biological clock cycle has been disrupted.
They also found mutant fruit flies with shorter and longer periods, so that there are three different biological clock performances: acyclic, short-period and long-period.
The gene that was screened out was named “period”(Period).
2017 Nobel Prize in Physiology and Medicine: Biological Clock
This has inspired many young scientists to join the ranks of research on biological clock genes, and three of them won the Nobel Prize in 2017.
Their work includes successfully cloned the cycle gene.
Through the cycle gene, they found a very important point.
If you want to complete the 24-hour cycle well, it is impossible to achieve it through one element. At least one element must be added to complete the “start-stop” process. They didn’t know what it was at that time. , So it is called the X factor.
Circulation in the cell
After 30 to 40 years of research, we now know that the X factor that can affect the biological clock far exceeds the original assumption.
The yellow block in the upper right corner of the figure represents the cycle gene.
It has a switch, which is genetically called transcription factor. The red box is the transcription factor Bmal1 and Clock.
These important proteins drive the expression of circadian clock genes, allowing the 24-hour “start-stop” to occur.
As you can see from the picture, these proteins are like timers, coming back to tell the switch when it should stop.
It also assists timekeeping through multiple proteins, provides time details to cells like a network, and completes biological clock and metabolic cycle regulation.
24-hour biorhythm
There are biological clocks in our liver and fat tissues.
It is equivalent to our tendency to accumulate energy during the day. When we eat a lot, we store energy in fatty tissues as fatty acids, as well as glycogen in the liver.
If such a process does not have a circadian clock gene well established within the scope of a day, it will cause a disorder of the circadian rhythm.
There are many ways to disrupt the biological clock, such as lack of sleep or eating a meal before going to bed.
More and more studies have found that the consequences of circadian clock disorders can lead to the occurrence of many diseases, such as diabetes, metabolic diseases, and aging.
The length of time humans sleep
Is the length of time a person sleeps reasonable? Are we sleeping too much?
Different creatures sleeping pictures
Let me show you the sleeping time of various creatures. The upper part of the picture represents the creatures that sleep during the day, and the lower one represents the creatures that sleep at night.
People sleep about 8 hours a day in the middle.
There is a very interesting phenomenon, large mammals sleep very short time.
The horse sleeps for two or three hours; the giraffe is very short, only 30 minutes to one hour a day; the elephant sleeps for 4 hours; the sperm whale sleeps for one or two hours. How do sperm whales sleep? It sleeps standing upright, and floats to sleep vertically in the sea very easily.
In small animals, mice sleep for 12 hours.
Why do small animals sleep longer, and large animals don’t need to sleep so long?
This is a very interesting biological subject that has not been completely solved yet. There must be interesting answers waiting for us in the future.
Optimal sleeping range
This picture shows how long sleeps are reasonable for different age groups. From the infantile period on the far left to the old age.
6～13-year-old children should sleep 9-11 hours a day, adults 7-9 hours.
Sleep well is also related to learning effects, and the relationship between sleep and learning will be mentioned later.
Famous people’s sleep time
When the sleep is less or even below the proper range, less than 6 hours, if you feel that you are still awake and make good work judgments, congratulations to all of you, like the celebrities in the picture, have special physiques .
They all sleep very short.
Da Vinci only slept for 2 hours a day; Napoleon lay down and slept for three or four hours, but would take a nap during the meeting, generally no more than 5 hours.
Edison is a very special person. I want to say that he is the person who destroys our natural rhythms most comprehensively.
Why? Because he invented the light bulb, it added the harm of light pollution to the night of modern civilized society.
Besides, he doesn’t like sleep himself.
He once said, “Sleep is a waste of time, a continuation of the barbaric age of cave dwellers.”(Sleep is a criminal waste of time, and aheritage from our cave days). So his attitude towards sleep is contemptuous and paranoid.
Mrs. Thatcher also slept very little, about 5 hours a day. She believed that “sleep is for the weak”(Sleep is for wimp).
Here I remind everyone of a correct concept: Sleep is absolutely important, and good sleep is the foundation of health.
The above-mentioned celebrities neglected sleep because of their special physique and their sense of responsibility.
Mrs Thatcher got Alzheimer’s disease in her later years. Is this disease directly related to sleep?
I think so, so sleep is very important.
How do most people sleep a day?
There are two main ways: one is to lie down and sleep for more than 7 hours at night, and the other is to sleep for 30 minutes at noon after lunch if possible.
People often do more things to save time by doing so-called short sleeps and intermittent sleeps. In fact, this still depends on your physique.
Da Vinci mentioned earlier, he divided the day into 6 pieces, and slept for 20 minutes after every 4 hours of work, adding up to sleep for about two hours a day.
But many friends who believe in “Da Vinci Sleep” try to do it on their own, and they can’t make it for a week, and the “sleep debt” incurred will last for a whole week.
By the way, our national treasure, the giant panda, is an example of a special physique. The food it eats is very boring and nutritious.
It takes more than 14 hours to eat bamboo every day. You always have to take a break from eating so much bamboo, so it is easy to have 4 short sleeps like eating for a while and sleeping for a while.
Speaking of special physique, do you have any special physique?
We can learn about our own living conditions. Some people are indeed different from ordinary people in their daily routines because of genetic mutations.with. Two more important examples:
One is “early bird”, that is, early sleep syndrome. What are the symptoms of early sleep syndrome?
I went to sleep immediately after eating dinner, and then got up in the middle of the night. If you want to call a friend, basically no one answers, which seriously affects the social interaction.
This mutation is related to the mutation of cycle gene number 2.
The other is “night owl”, which means delayed sleep syndrome. The time to go to bed is after 3pm, and the time to wake up is noon.
There is no specific research to prove whether these special physiques have health risks, but this will definitely affect their social life and work efficiency.
This is evidence that circadian clock genes affect sleep time.
How to detect sleep
How do we study sleep?
The electronic bracelet is very convenient now, and it is easy to study sleep after wearing it.
Actually, the data we get when we wear an electronic bracelet are active and inactive data, which is used to indirectly determine how long we sleep at night.
The most important way to study sleep is to assess the quality and depth of sleep by studying brain waves. Stick electrodes on the scalp and watch the electrical discharge in the brain.
The picture shows beta waves and alpha waves.
When the discharge per unit time is very frequent, it means that we are relatively awake and our brains are thinking.
When the waves come slower and slower, especially like delta waves, which oscillate once or even less than once per second, the interval becomes larger and the waveform becomes slower and slower, which means that the entire sleep has entered the deepest state. , Also called slow wave sleep.
This is the monkey sleep data recorded by Dr. Qiu Peiyuan and Jiang Jian of our team. They carefully sorted the monkey’s sleep data into 20 minutes of turning on the lights and 40 minutes of turning off the lights.
Observe how it goes to sleep. We shortened this hour’s sleep record into a 1-minute short video.
You can see the process of switching from β wave and α wave to slow wave all the way in the video, and the interval between them is getting bigger and bigger.p>
People will definitely generate some learning signals when they are active every day.
The upper picture on the left is the daytime state, which will produce learning signals and also produce irrelevant signals.
For example, if you come to the SELF forum today, hearing topics related to biological rhythms will generate learning signals. Before coming, someone was afraid of being thirsty and bought a bottle of water, which is more like an irrelevant signal.
When extracting information afterwards, you don’t need to think about buying a bottle of water to think about biorhythms.
It is more about strengthening the biological rhythm of “how does the biological clock start”, “Mimosa-related experiments”, and then slowly strengthening the learning.
The process of synapse formation
See the picture above for details. When the yellow neuron decides to combine with the new information (red neuron below), it will use a button-like method String together, this is the process of synapse formation.
The things that should be forgotten, like the orange connection above is disconnected.
Relatively messy things, such as “what did you eat last Tuesday night”, are easy to trim off at night, because they are not related to knowledge-related declarative memory.
Sleep is also for repairing. The greater the intensity of our brain activity and the greater the intensity of our work every day, we tend to produce some “waste”.
The faster we metabolize, the faster we produce waste. When waste is more and more, the brain has to rest, so sleep time is directly proportional to the metabolic rate.
There is an example to illustrate. The picture on the left shows that the metabolic speed of elephants and mice is 12 times different. This causes elephants with slow metabolism to sleep about 4 hours a day, while mice with fast metabolisms have to sleep. 12 hours.
Humans are between large animals and small animals. They require a higher metabolic rate than elephants, but much lower than mice. They need to sleep for 8 hours a day.
Of course, more experiments will lead to better answers. Basically, the function of sleep is trimming and repairing.
Biological clock imbalance
There are many diseases related to biological clock imbalance, such as sleep disorders, metabolic diseases, cardiovascular diseases, etc., and tumors and neurodegenerative diseases are all related.
The imbalance of the biological clock can cause chronic diseases and accelerate aging.
The above phenomenon is a phenomenon of normal aging. If it is premature aging, when degenerative diseases occur, there will be more circadian clock disorders. Sleep activity graph The healthy elderly do not move very much during the night and sleep well. But if you have Alzheimer’s disease and Huntington’s disease, their biological clock is completely disordered and their activity level is also affected. Said to be a state of waking up at any time. Parkinson’s disease is the same situation, if the activity spectrum is drawn, it is very similar to Alzheimer’s disease. Some studies have found that the level of melatonin in the blood of Parkinson’s patients is indeed relatively low. The light blue line is the content of melatonin. In addition, the level of the pair switch BMAL1 just mentioned has also dropped. Overall, we can see that in the clinicalIn the research, when there is a problem with the biological clock, the connection with the outside world becomes weaker and weaker. In experiments in mice, it can be seen that when key biological clock genes are knocked out, a series of chronic diseases will be caused. The most difficult to verify is depression, emotional-related mental diseases. Will sleeping well affect mood? We know it will. But the key is whether there is a genetic basis to prove this matter. For example, we know that the light time in northern Europe is only 5 hours in winter, which is prone to seasonally related depression. After drawing blood from depressed patients, we can see that there are many genetic variants of the biological clock involved in the occurrence of depression. . Why do you need a monkey model If we want to use the biological clock to understand the whole thing, and use the biological clock-related intervention to try to treat sleep disorders, metabolic diseases, etc., it is obvious that the current model is not enough. So, we need to add biological models other than mice. We know that fruit flies and mice have made a lot of contributions to the research of biological clocks, and the monkey model is also expected to make a good contribution to our future interventions in circadian clock disturbances and sleep disturbances. Why do you need a monkey model? One of the reasons is that the mice turn upside down day and night, and the reaction of seeing or seeing the light does not simulate the state of mental illness such as depression. In addition, the expression curve of the biological clock mentioned earlier, such as genes Bmal1 and Per1, can obviously be seen that mice and primates express day and night are also opposite. So our team at the Institute of Neurology has done a very important job recently. We made the world’s first circadian clock disorder monkey model. This model is the result of the hard work of the Institute of Neurology. Here we knock out the important biological clock switch BMAL1. We know that its biological rhythms will be chaotic, and we also know that its sleep will be shortened, but we were surprised to find that it is around 1 year old (equivalent to children Around the age of six or seven) a circadian disorder occurred. It’s easy to wake up before the light is turned on, about 3 hours of sleep a day is lost. We use EEG recordings to analyze how long it sleeps. Originally, normal slow wave sleep in monkeys should be about 26%, and rapid eye movement sleep at about 8%. Both sleeps of BMAL1 knockout monkeys are shortened, and the overall sleep time is only 20%. The length of sleep time of wild king monkey and knockout monkey This is very similar to the premature aging just mentioned. The amount of sleep has reached the amount corresponding to the retirement age. In addition, I just mentioned a problem that is more difficult to prove. Will the circadian clock disorder caused by circadian clock gene knockout directly lead to emotional diseases? We try to analyze its depression and anxiety phenotypes. The most classic experiment is to put both normal monkeys and knockout monkeys in a new environment. Because the new environment is bigger, cleaner, and more beautiful, normal monkeys will be very excited, so they will be exploring behavior in 20 minutes. The red part in the picture is a 20-minute trajectory. It is very happy to see this new home. Knock the monkey depression into a new cage, and dare not explore the environment without harming it. It stayed in the corner farthest from the walkway for 20 minutes, and even if it moved, it would choose to climb up to see if the environment would be harmful. Cortisol in wild monkeys and knockout monkeys It has too many worries and is not interested in new things. This is the scope of depression and anxiety. Through experiments, we have found that the circadian clock disorder does cause the phenotype of depression. Through the video, we can see that normal monkeys are curious about humans, they can look at people, and they can also eat fruits they give. But knockout monkeys will be very scared when they see people, and they will only hold their heads. Even if you look at it with an apple, it tends to hold it and eat it after you put it down. This is a good proof that biological clock genes and circadian clock disorders cause mood diseases. In the future, we want to use the monkey model to do a series of interventions, whether it is degenerative diseases or diseases related to metabolic aging, Or depression, we all hope to be able to achieve it in the monkey model. We will continue to conduct research to share more important findings with you. Finally, I hope you all sleep well every day and maintain your own biological clock. Thank you all! This article is from WeChat official account:Gezhilundao Forum (ID: SELFtalks) , author: Zhang Hongjun