Is it possible to adjust the circadian rhythm
How our biological clock works: is there a "sleep pill"
If you have ever made long flights from one time zone to another, then you know perfectly well what discomfort jetlag (from the English words jet - jet plane and lag – lag) brings – jet lag syndrome. It is usually accompanied by fatigue, insomnia, headache, loss of appetite and other unpleasant things.
Why is this happening? With the rapid change of time zones, the natural daily rhythm (the change of day and night) comes into conflict with our circadian rhythm – the internal "clock" of the body. They represent cyclic fluctuations in the activity of various biological processes – changes in body temperature and blood pressure, hormone production, and the functioning of internal organs. It was possible to show that circadian rhythms have an exclusively internal nature only in the 1980s by sending Neurospora crassa mushrooms into orbit: they did not change circadian rhythms, even when researchers imitated an hour and a half a day with the help of lighting. This meant that the biological clock does not depend on external light or, for example, geophysical signals. However, to some extent they are still affected by one external factor – the length of daylight.
Is it possible to "translate" circadian rhythms so that the consequences of the flight from Moscow to Vladivostok pass quickly and painlessly? Scientists have been investigating this issue (and the daily fluctuations in the activity of the body themselves) for more than a dozen years. In 2007, Argentines Patricia Agostino, Santiago Plano and Diego Golombek were awarded the Nobel Prize in the Aviation category. They found that hamsters recover faster from jetlag if they are given a substance called sildenafil, known by the trade name "Viagra". Initially, sildenafil was synthesized as a drug to improve blood flow in the myocardium and treat angina and coronary heart disease. However, during clinical trials, it was found out that the effect of sildenafil on cardiac blood flow is minimal, but it has a pronounced effect on blood flow in the pelvic organs.
But back to the hamsters. All the animals were raised under artificial lighting: the daylight lasted 14 hours, and the night lasted 10. Then the hamsters were placed in separate cages, each of which had a running wheel (in order to better record the hours of rodent activity). After a 10-day stay in cages and getting used to running wheels, hamsters were given a six-hour "time zone shift" that lasted for several weeks: the lighting mode of the cages changed the way a person's daily rhythm would change when flying from New York to Paris (that is, from west to east, with the clock moving forward). At the same time, one group of test subjects received a portion of Viagra on the day of the "clock transfer", and the second did not. Scientists have found that sildenafil in a dosage of 10 micrograms per kilogram of the body helped hamsters to restore downed circadian rhythms 50% faster. Smaller dosages of "Viagra" worked worse, but still slightly accelerated the transition to normal functioning of the body.
Diego Golombek believes that sildenafil helped hamsters cope with jetlag because the content of a molecule called cyclic guanosine monophosphate (cGMP) increased in the body. According to the scientist, this accelerated the biological clock of the animals for some time. This also explains the fact that Viagra did not help rodents cope with jetlag when simulating a flight from east to west: thanks to the drug, accelerated circadian rhythms "caught up" with the time difference, but the drug cannot turn the biological clock back.
Although the authors of the work considered sildenafil as a likely cure for jetlag for humans, relevant studies have never been conducted. However, in 2013 Skyscanner – a system for searching for air tickets – conducted a survey among its users. About a thousand Singapore Airlines passengers took part in the survey – 11% of them reported that they had tried taking Viagra as a remedy for jetlag, and 5% said that the drug really helped to cope with jet lag. This, however, in no way indicates the effectiveness of sildenafil, and scientists recommend taking a blue tablet from jetlag only if two conditions are met: you are a hamster, and you are flying from west to east.
Despite these disappointing news, let's still figure it out: are there effective methods to combat jetlag? And at the same time, we will find out exactly how our body regulates the biological clock. The first question in 2017 was answered quite unambiguously by Michael Rosbash and Jeffrey Hall, the winners of the Nobel Prize in Physiology or Medicine of that year.
Michael Rosbash:
There is no therapy or medication that would really help to "reset" the circadian rhythms.
There are, of course, medications that are recommended for jetlag, but they help some people, others don't, so I can't say that they are effective. The best thing to do with jetlag is to sleep.
Jeffrey Hall:
We don't know how to "reset" our biological clock.
The circadian rhythms of a person are approximately equal not to 24 hours, but to 24 hours and 15 minutes. For these 15 minutes, our body resets circadian rhythms daily, but no more. We can't handle the time difference between time zones. And it is unknown exactly how the "reset" mechanism works.
Michael Rosbash, Jeffrey Hall and the third winner Michael Young were awarded Nobel Prize in 2017 for "the discovery of molecular mechanisms that control the circadian rhythm" – the same biological clock. However, they did not discover the first piece of the genetic mechanism of circadian rhythms. This was done in the 1960s and 1970s by Seymour Benzer and Ronald Konopka, who created mutant fruit flies with altered circadian rhythms: some had 28 hours, others had 19 hours, and others had no rhythm at all. The same gene was broken in all insects, which means that in an unchanged state it was responsible for maintaining a normal, 24–hour, daily rhythm. Scientists called the gene per, – from the word period, "period". The next step in the study of biological clocks was taken by Rosbash, Hall and Young.
Genes contain a lot of different information, including about the structure of proteins – for simplicity, we can say that the genes have a "recipe" for their manufacture (that is, genes encode proteins). Jeffrey Hall and Michael Rosbash investigated the relationship of the per gene with its PER protein and found out: at night, the protein level reaches its maximum concentration, after which it blocks the work of its own gene, stops synthesis, and then decays during the day. But in order to "turn off" the gene, the protein must penetrate into the cell nucleus – after all, it is there that the genetic material is stored. Hall and Rosbash were able to show that protein accumulates in the nucleus at night, but could not figure out how it gets there. This was done by Michael Young – in 1994 he discovered the second gene of the biological clock called timeless (translated from English – "timeless"). Yang's lab found out that the cycle of this gene is also equal to 24 hours, and it encodes the TIM protein, which directly binds to PER, helps it penetrate into the nucleus and does not allow it to break down.
This feedback mechanism explains exactly how the daily fluctuations in the activity of our body are regulated. Of course, there are many other tools that are involved in the work of the biological clock (for example, the doubletime gene, also discovered by Yang, delays the accumulation of the PER protein and adjusts circadian rhythms so that they coincide with the natural cycle of day and night; the cry gene, which under the influence of light destroys the TIM protein, after which the remaining one is destroyed "partner" PER, and many others). These discoveries revolutionized the understanding of the key mechanisms of the human biological clock.
As for the most effective medicine for jetlag (in addition to sleep) – opinions differ here. Someone believes that purposeful preparation of the body for the upcoming change of time zones works best (for example, a gradual change in the daily routine a few days before the trip, an attempt to sleep through most of the flight or, conversely, arrange a 24-hour sleepless marathon); someone advises not to eat heavy food, someone – drink more alcohol or, conversely, drink nothing but water. All such recommendations, as a rule, are based on a person's personal experience – and it is not necessary that they will help you. And some tips can worsen your well–being - a day without sleep has never made anyone more cheerful, and alcohol is harmful in any doses.
Very often, to normalize circadian rhythms, it is advised to take melatonin, a hormone of the pineal gland that controls our biological clock in response to changes in the rhythm of lighting. Melatonin levels change in the body with a frequency of 24-25 hours, reaching a maximum between midnight and eight o'clock in the morning. Young children have the largest amounts of melatonin in the blood, but with age the level drops significantly. Therefore, babies sleep a lot, and the elderly suffer from insomnia.
Melatonin-based drugs are not allowed in all countries: for example, in Australia they can only be prescribed to people over 55 years of age to restore sleep, in the USA melatonin-based drugs are prohibited as medicines and fall into the category of dietary supplements, but they cannot be used as part of food. However, drugs of this type have been studied quite well, and the results of research have been published in hundreds of scientific articles. Scientists have concluded that melatonin significantly increases sleep time in people over 55 years old, helps them fall asleep, does not cause side effects and addiction. In the review of night shift work, scientists were able to find only weak evidence that melatonin increases the duration of daytime sleep. But for the fight against jetlag, it really turned out to be very effective – however, this conclusion was made on the basis of only eight studies.
So melatonin, although it works, does not promise miracles: it can help you fall asleep early and reconfigure the daily routine to a different time zone, but unfortunately, there is no way to overcome lack of sleep. By the way, if you do not want to take the drug itself, try eating bananas, grapes or other plant foods before going to bed – melatonin is found in many fruits and fruits, although, of course, not in such quantities as in the medicine. And remember about the receptors on the retina of the eye: when it's light around, melatonin is produced in smaller amounts, so blackout curtains will really help you fall asleep.
Portal "Eternal youth" http://vechnayamolodost.ru