Cancer and biorhythms
Biological clock against cancer
Kirill Stasevich, Science and Life (nkj.ru )
Biological rhythms are not only the alternation of sleep and wakefulness, they are also daily changes in the hormonal background, in metabolism, in the immune system. It is difficult to find what biological rhythms do not affect in our body. Therefore, is it any wonder that when they break down, it is fraught with various chronic diseases. Failures in the biological clock contribute to the accumulation of excess fat and concomitant metabolic problems, up to diabetes, contribute to cardiovascular diseases, increase the likelihood of cancer. But if you try to fix a broken watch, then the chances of getting sick with something unpleasant will decrease.
When we hear that a malfunction in the circadian rhythms contributes to obesity, we need to remember that these things are mutually conditioned – that is, overweight in itself can spoil the biological clock. Maybe a person will not immediately feel that something is wrong with his watch, but changes in the level of activity of genes, hormones, etc. will happen one way or another. It is known that obesity increases the risk of breast cancer, and it is believed that this increase in risk occurs through a broken clock.
Another factor that increases the likelihood of breast cancer is menopause, which is associated with a strong hormonal restructuring. During menopause and obesity, the body cells develop resistance to insulin, which, in turn, affects metabolism. The synthesis of insulin and its level in the blood no longer obey any rhythms, the body tries to keep the insulin level consistently high in order to somehow keep the amount of sugar in the blood under control. Usually, insulin resistance (or insulin resistance) and elevated blood sugar are talked about in connection with type 2 diabetes. But high levels of insulin are also associated with cancer.
The staff of the University of California at San Diego experimented with mice that imitated menopause (just in case, let's clarify that mice, like almost all animals, do not have menopause, so for such laboratory experiments it is necessary to create special mice with menopause, as it were). In addition, the experimental mice were overweight. Some animals could eat anything during the day. Others were kept on low-fat feed, which again was available for 24 hours. Still others were simply limited in food by time: they only had food for eight hours at night (when mice are active). All the mice had a breast tumor.
In those who could eat at any time of the day or night, the tumor grew faster and spread metastases more actively. The type of feed did not play a special role – a fatty diet also contributed to cancer, as well as a low-fat one. But in those mice that ate only for a certain time, the tumor grew poorly and was less aggressive. The same results were obtained when the level of insulin in the blood was artificially increased and lowered in animals: with increased insulin, cancer became more dangerous.
In an article in Nature Communications (Das et al., Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in these postmenopausal mouse models), the authors say that even such a not very strict restriction of food intake in time helps to normalize insulin levels, and, as a result, reduce the risk of a malignant tumor. Forcing himself to eat only at a certain time, the individual restores the daily rhythm in the work of insulin and a large block of metabolism. It's not so much what you eat that matters here, as when: let the food be with the usual fat level, but let it be only at a certain time. The mice could only eat at night when they were active. We have an activity time of a day, so perhaps to reduce the risk of breast cancer, it is worth allocating a certain period for eating during the day, and not eating anything either before or after. But here we should not forget that the experiments were performed on special mice, and it is worth waiting for specific clinical recommendations here – in the sense that for people the antitumor schedule of breakfasts, lunches and dinners needs to be developed separately. In addition, in this case we are talking about breast cancer, which occurs against the background of obesity and menopause.
Another example of how cancer can be affected through a biological clock is described in another recent article in Nature Communications (Shafi et al., The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair). Thomas Jefferson University researchers have noticed that the level of CRY-1 protein increases in human prostate cancer cells, especially in the late stages of the tumor. CRY-1 is one of the main regulators of circadian rhythms. He has many spheres of influence, in particular, he regulates DNA repair. When the DNA of cancer cells deteriorates greatly – for example, during radiotherapy – the level of CRY-1 in them sharply increases, which mobilizes repair proteins so that they correct mutations.
Many types of chemo and radiotherapy are aimed at damaging the DNA of cancer cells as much as possible, so that they will not survive after that. But it happens that cancer cells easily tolerate both chemo and radiotherapy. It is quite possible that CRY-1 helps them here, thanks to which DNA damage quickly disappears. Why CRY-1 levels rise in the late stages of cancer is still unknown. It is possible that cancer cells, as the disease develops, are able to control the activity of the CRY-1 gene. It is possible that the CRY-1 level is getting out of control for some other reason unrelated to cancer. It would also be interesting to know how things are with CRY-1 in other types of tumors. Anyway, prostate cancer can be made more sensitive to treatment by acting on the CRY-1 gene and protein, this out-of-order spring of the biological clock.
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