Disturbances in the biological clock increase the likelihood of cancer

Kirill Stasevich, "Science and Life"

Our physiology is tuned to a regular change of day and night: so, during the day, you can notice fluctuations in the hormonal background (the level of some hormones – for example, growth hormone – increases at night, while others – such as glucocorticoids – peak before waking up), and if you go from the level of hormones and tissues to the level of cells and genes, then and there we will see how some genes turn on and off at certain times of the day.

These processes are controlled by a system of biological clocks that inform genes, cells and tissues about what time of day it is in the yard. Considering how much depends on the serviceability of such watches, it is not surprising that violations in their work affect our health.

And it's quite easy to spoil them – it's enough to go to bed at different times, arrange sleepless nights in front of the computer, or just regularly cross several time zones. The biological clock is unable to turn off our consciousness and forcibly send us to sleep, therefore, while we are awake, they continue to maintain "daytime" genes, hormones, etc. in working order, as a result, the schedule of molecular and cellular activity is out of schedule, leading to a variety of unpleasant consequences.

The disturbed daily rhythm affects not only the higher nervous activity, but also, for example, the metabolism: going to bed at the wrong time or regularly not getting enough sleep, you risk getting diabetes, overweight problems, etc. There are many works on this topic (so, last year we wrote about why artificial light makes you fat), however, often everything is limited to statistics, albeit quite convincing, but not describing specific processes in cells.

Researchers from the Massachusetts Institute of Technology in their experiments managed to show exactly how the causal relationship between circadian rhythm disorders and the likelihood of developing a cancerous tumor works (Why working the night shift can pose a cancer risk).

It is known that in mammals, the biological clock of the whole body receives information about the time of day from special cells in the retina of the eye, the signal from which goes to a special area of the brain called the suprachiasmal nucleus. From here, the "clock" information is scattered through the cells of the body through hormones and other signaling molecules.

In cells, it is taken by the Bmal1 gene, which regulates the activity of other circadian genes, including the Per2 gene. During the day, the number of proteins encoded by Bmal1 and Per2 falls and rises, but if the daily sleep-wake rhythm is disrupted, then the molecular periodicity of Bmal1 and Per2 proteins will also be disrupted – their concentration will rise and fall irregularly.

As it turned out, the unregulated activity of Bmal1 and Per2 makes the malignant tumor more aggressive. Talis Papagiannakopoulos and his colleagues subjected mice to systematic jetlag, that is, they kept the animals in the light for an extra 8 hours every two to three days. Just in case, let's remind you that mice are active at dusk and at night, so daylight for them is the same as night for us; nevertheless, such a schedule, with the night lengthening from time to time, was equivalent to if mice worked the night shift to get some sleep later during the day, or they traveled through several time zones.

The animals were initially predisposed to one of the types of lung cancer, in the sense that they were already very likely to develop it, however, as the authors of the work in Cell Metabolism (Circadian Rhythm Disruption Promotes Lung Tumorigenesis) write, in mice with an upset circadian rhythm, the tumor appeared even faster and turned out to be more aggressive.

In another experiment, mice with the usual 12-hour alternation of day and night, but at the same time, the clock genes Bmal1 and Per2 were turned off. The results were the same – cancer appeared and grew faster than with working genes. The reason here is that Bmal1 and Per2 control the work of a very well-known gene c-myc, which stimulates cell division.

If c-myc is constantly active in a cell, the cell turns into a malignant one, and mutations in the c-myc gene that allow it to be constantly active are found just in cancer cells. Bmal1 and Per2 make sure that c-myc does not work all the time, but if something happens to Bmal1 and Per2, c-myc will provoke a tumor. At the same time, a mutation does not necessarily have to get into the circadian genes – their work can be disrupted without any mutation, simply by upsetting your daily routine.

Figure from an article in Cell Metabolism – VM

Of course, this does not mean that if you go to bed late and get up early, you will inevitably have cancer – here we can only say that the probability of the disease will increase. However, malignant tumors arise due to many factors, and it may happen that all other factors are already in place, and the last drop is missing, which may just be a disturbed circadian rhythm.

Researchers, by the way, checked how things are with Bmal1 and Per2, as well as other daily genes, in people with lung tumors – as expected, their activity of such genes was reduced, and the worse they worked, the more aggressive the tumor was. So the results obtained make sense not only for mice.

It is also worth clarifying that we are talking about the disordered course of the biological clock. That is, those "owls" whose daily regime remains constant, even if not the same as the regime of "larks", probably will not have problems with unregulated circadian genes.

Trouble, obviously, awaits those whose day and night are getting shorter, then longer, and sometimes they change places from time to time. However, we must hope that we already know enough about the structure of circadian rhythms to create some kind of therapeutic method for their correction.

Portal "Eternal youth" http://vechnayamolodost.ru  23.08.2016