Gene – “alarm clock”: how the biological clock works

Have you ever been surprised why we wake up in the morning even if the alarm clock is off and there are no extraneous noises? To study the mechanism of a kind of “miracle of nature” took specialists from the Salk Institute for Biological Studies. They dismantled the biological clock by a small screw and revealed a completely new component of their device – the gene responsible for starting our internal alarm clock.

“Our body is essentially a collection of watches,” boldly states Satchindananda Panda, associate professor at the Salk Institute’s Normative Biological Laboratory. In September this year, together with his colleagues, he published a report in the journal Nauka, in which he explained in detail how the KDM5A gene encodes the JARID1a protein, which serves as the activation switch for biochemical processes that support our circadian rhythm. 

Let’s try to figure it out. The daily cycle of sleep and wakefulness is controlled by special molecular mechanisms. One of the central links in the process was the PERIOD protein (PER). The number of PER proteins in any of our cells rises and falls rhythmically every 24 hours. As a result, the level of this substance is used by the body as an indicator of the time of day and, by the way, it is PER that dictates to us when to sleep, and when to stay awake. The amount of protein progressively increases during the day, reaching its peak in the evening. At this moment, the concentration of PERIOD in the cells is so high that it activates the work of two genes: CLOCK and BMAL1. After this, the protein level in the body begins to decline rapidly. Along with it, various biological systems slow down their work: blood pressure drops, heart rate and brain activity decrease. Until now, it remained unclear how each morning the protein level rises again, activating the body. Scientists from the Salk Institute for Biological Research just answered this question by presenting a new type of enzyme, JARID1a, to the audience. Its appearance is a kind of “horn call” for cells and organs that should “wake up” at dawn. Fruit flies and mice, whose cells were genetically modified in such a way that JARID1a products were blocked, literally lost track of time: they did not know when to sleep, and when to stay awake, they often and briefly dozed both day and night. The level of PER protein in them was constantly maintained at low positions. Thus, Satchindananda Panda and colleagues found that every morning, JARID1a reactivates the CLOCK and BMAL1 genes by increasing the level of PER protein. 

Scientific value . Now that the scientists have managed to understand why we wake up every day, they can continue their research by trying to calculate the role of JARID1a in sleep disorders and the occurrence of chronic diseases. The new gene can be used as a target for drugs. An interesting solution to the problem of insomnia in the elderly. Obviously, the biological clock “gets lost” with age, but the mechanisms of this process until recently remained unexplored.

The discovery of the activating enzyme has been scientifically proven: 24-hour work shifts (for example, for nurses and emergency personnel) disrupt normal sleep and wake cycles, increasing the risk of a number of diseases. The fact is that complete metabolic cell cycles are fundamental for the adequate functioning of genetic mechanisms that control, including cell growth and division, which is especially important in the development of cancer.

The cellular mechanisms of diabetes , another chronic disease, are also associated with metabolic cycles and are controlled by a biological clock. For example, the conversion of sugars to fat usually occurs in healthy people only at certain times of the day, and in those with diabetes, such transformations are likely to occur all day.

Ultimately, the discovery of JARID1a could lead to new treatments for insomnia, cancer, diabetes, and other chronic diseases.

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