Content:

• How to take Melatonin 10 Mg for weight loss, which type of protein is better
• Melatonin Depression: the benefits and harm, the use of diabetes instead of sugar

Aging fork

The change of day and night, light and darkness is one of the most significant natural phenomena on Earth. The rotation of our planet around its axis and at the same time around the Sun counts the days, seasons and years of human life. The biological clock of the body is the epiphysis (pineal gland), its hormone melatonin can be likened to a pendulum, which ensures the course of these clocks. It is difficult to overestimate the role that our natural chronograph plays in the regulation of the physiological rhythms of the body and their adaptation to environmental conditions …

The honor of discovering this hormone belongs to A. Lerner, a dermatologist at Yale University. In 1953, he managed to isolate an extract from bovine epiphyses, due to which the frog’s skin became lighter. The researcher and his colleagues reworked 250 thousand epiphyses to get a key component – the active substance, which was identified as N-acetyl-5-methoxytryptamine.

The discoverer gave the new hormone a more romantic name “melatonin” (from the Greek words melas – black and tosos – work) and presented his discovery to the public in a one-page article published in 1958 in the Journal of the American Chemical Society.

Our “sundial”

Epiphysis, a neuroendocrine organ whose main function is to transmit information about the light regime of the environment to the body’s internal environment, is found in all vertebrates.

It should be noted that extrapineal melatonin is present in the body, that is, melatonin synthesized outside the epiphysis. The discovery of the latter is connected with the Russian scientists N. T. Raikhlin and I. M. Kvetniy, who in 1974 found that the cells of the vermiform process of the intestine also have the ability to synthesize melatonin. It was found that melatonin is formed in other parts of the gastrointestinal tract, as well as in the liver, kidneys, gall bladder, ovaries, placentas, thymus, in blood cells (leukocytes, platelets), etc. The biological effect of extrapineal melatonin is realized directly there where it is synthesized.

Perhaps the most accurate would be a comparison of the epiphysis with the sundial, in which melatonin plays the role of a shadow from the gnomon – the rod, which serves to determine the height of the sun. During the daytime the luminary is high and the shadow is short (respectively, the level of melatonin is minimal), with the onset of darkness, the synthesis of melatonin by the epiphysis and its secretion into the blood increase. Thus, the concentration of melatonin has a daily rhythm determined by the chronological metronome – the rotation of the Earth around its axis.

As part of the body’s daily rhythm, melatonin maintains the body’s sleep-wake cycle, as well as daily changes in physical activity and body temperature. Its concentration in the blood reaches its maximum 1–2 hours before awakening: it is at this time that the person’s sleep is the deepest, and the body temperature reaches its minimum.

Electricity, which entered our lives more than a hundred years ago, radically changed the light mode. The effect of light on a person at night, often called light pollution, has become an essential part of the modern lifestyle, characterized by many serious behavioral and health disorders, including cardiovascular diseases and cancer. According to the hypothesis of circadian destruction, prolonged use of additional illumination disrupts the internal circadian rhythm, suppresses the melatonin secretion in the night, which leads to a decrease in its concentration in the blood.

Night guard melatonin

It has been shown that illumination of 1.3 lux monochrome blue light (or 100 lux white light) can significantly suppress the production of melatonin by the epiphysis. A significant decrease in melatonin levels was found in volunteers who were subjected to intermittent exposure to light at night for two weeks.

The molecular clock mechanism of the suprachiasmatic nucleus of the hypothalamus (the neurons of which transmit light information to the epiphysis) is based on the interaction of positive and negative feedbacks between the work of several, at least nine, main “clock genes” providing the circadian (circadian) rhythm. Light has been found to directly affect the expression of some of these genes. The same, in turn, regulate the functions of key genes in the cell cycle and apoptosis genes. Mutations in some clock genes dramatically affect many functions of the body and lead to the development of various pathological processes.

An artificial increase in the duration of the light period during the day, even by 2-4 hours, in rodents leads to an increase in the duration of the estrous cycle, and in some cases to its disturbance. If the exposure of light to mice and rats is increased to 24 hours a day, most of them will develop persistent (permanent) estrus syndrome in a short time. Under natural conditions, this syndrome develops at a later age and then turns into anestrus, which is the physiological equivalent of menopause in women.

In the ovaries in rats with persistent estrus, follicular cysts and ovarian tissue hyperplasia are found, and there are no yellow bodies in them. Cyclic hormone production, characteristic of the normal reproductive period, is disturbed, leading to hyperplastic processes in the mammary glands and uterus.

And the rats in this respect were not so far from humans. There is evidence that additional lighting at night shortens the duration of the menstrual cycle in women with a long (more than 33 days) cycle. Thus, in 60% of surveyed nurses with a regular menstrual cycle and frequent night shift work, the menstrual cycle was shorter than 25 days, and about 70% of nurses complained of rare or frequent dysmenorrhea (absence of menstruation).

The use of constant illumination leads to an increase in the sensitivity threshold of the hypothalamus to the inhibitory effect of estrogens – a key mechanism in the aging of the reproductive system in both female rats and women. Thus, additional night-time lighting contributes to the acceleration of age-related extinction of female reproductive function.

How to take Melatonin 10 Mg for weight loss, which type of protein is better

The main functions of the pineal gland in the body

• Regulation of circadian and seasonal body rhythms

• Regulation of reproductive function

• Antioxidant protection of the body

• Antitumor protection

• “Sundial aging”

In rats with persistent estrus, a decrease in glucose tolerance and insulin sensitivity was also found. In addition, the effect of constant light on the body increases the intensity of lipid peroxidation in animal tissues, while the use of melatonin causes its decrease, especially in the brain.

The antioxidant effect of melatonin was discovered by an American scientist R. Reiter in 1993. It is due to the pronounced ability of melatonin to neutralize free radicals, including those that are formed during lipid peroxidation, and the fact that glutathione peroxidase, a powerful endogenous enzyme factor, is activated in its presence protection against radical oxidation.

Over the past 20 years, it has been established that melatonin plays a crucial role in the regulation of the body’s immune defenses, including in the implementation of antitumor immunity. To date, it has been proven that melatonin receptors are present on the membranes of many immunocompetent cells. Removal of the epiphysis or the use of drugs that suppress the synthesis of melatonin, is accompanied by inhibition of antibody production, and its introduction stimulates the production of interleukins and g-interferon by lymphocytes.

Night work and cancer

The number of workers with night work or shift work reaches one-fifth of the total number of workers in the United States and in most EEC countries. The apparent deterioration in the health of such workers is associated with sleep disorders, gastrointestinal and cardiovascular diseases, metabolic disorders; an increased risk of diabetes is also possible.

Obesity, high triglycerides and cholesterol, as well as a low concentration of high density “anti-sclerotic” lipoproteins (HDL) have been shown to be more common in this group than in those working during the day shift. In addition, it has been proven that these indicators, along with hypertension, reduced blood fibrinolytic activity and glucose tolerance, are risk factors for not only cardiovascular diseases, but also malignant tumors. This is confirmed by data on a much larger number of deaths from malignant neoplasms in shift workers who have worked in production for at least 10 years, compared with workers employed only during the daytime.

An increased risk of developing breast cancer was established among nurses who have had experience of more than 30 years and work in shifts, which was accompanied by a decrease in the level of melatonin and an increase in the concentration of estrogens in their blood. High oncological risk is also characteristic of female flight personnel of airlines and women of other professions working on night shifts.

As early as 1964, the German researcher V. Johle discovered that the number of breast tumors and the deaths caused by them in mice kept in a room with round-the-clock illumination are significantly higher than in animals that were in the usual light mode. A similar pattern can be traced in relation to other tumors.

Two years later, I. O. Smirnova, an employee of the Cancer Research Center (Moscow), found that in the mammary gland of the overwhelming majority of female rats, seven months after the start of exposure to constant illumination, hyperplastic processes and mastopathies develop. According to I. A. Vinogradova (Petrozavodsk State University), when kept under constant light up to 18 months of age, slightly more than half of the female rats live to it, with standard light almost 90% of the rats. At the same time, spontaneous tumors were found in 30% of the rats of the first group, whereas among the rats kept in the standard lighting mode, such tumors were found only in 16%.

A similar effect from constant illumination was obtained in experiments conducted in our laboratory by D. A. Baturin on female mice carrying the HER-2 / neu breast cancer gene. In these animals, a greater number of multiple breast adenocarcinomas were noted compared with the group of females kept under standard lighting. It should be noted that the carcinogenic effect of constant illumination is proportional to the intensity of the latter.

In 1965, IK Khaetsky from the Institute of Oncology Problems (Kiev) for the first time reported on the stimulating effect of continuous illumination on the chemically induced breast carcinogenesis in rats. Subsequently, in a number of works by our and foreign researchers, the activating effect of constant illumination on the development of animal tumors of carcinogenic induced tumors of various localizations was proved.

At the same time, the effect of round-the-clock lighting does not have to be permanent. Thus, when conducting our experiments together with D. Sh. Beniashvili, rats subjected to transplacental exposure to the N-nitrozoethylurea carcinogen were kept in a room with lights on throughout pregnancy and feeding the pups, after which the offspring were kept in the normal light mode. It was found that even the short-term effect of constant illumination on rodents contributed to the future development of tumors of the nervous system and kidneys in them with the introduction of a carcinogen.

Melatonin Depression: the benefits and harm, the use of diabetes instead of sugar

A cure for time?

Thus, as a result of epidemiological and experimental studies, scientists have found that environmental and genetic factors that damage the systemic and / or local circadian rhythm can jeopardize the temporary regulation of cell division and enhance the growth of tumors. But this does not exhaust their negative effect on the body.

It should be noted that even under favorable environmental conditions, the level of melatonin production in the body does not remain constant throughout life. Thus, in people in the age group of 60–74, most of the physiological indices undergo a positive phase shift of the circadian rhythm approximately 1.5–2 hours ahead. In persons older than 75 years, there is often a desynchronization of the secretion of many hormones, body temperature, sleep, and some behavioral rhythms. With what it can be connected? With aging, the functions of the pineal gland are also inhibited, which is manifested, above all, in the disturbance of the melatonin production rhythm and in the decrease in its secretion.

The effects of constant lighting

• Inhibition of melatonin synthesis and secretion

• Increased prolactin synthesis and secretion

• Increase the threshold of sensitivity of the hypothalamus to inhibition by estrogen

• Induction of anovulation and ovarian cysts

• Stimulation of proliferative and tumor processes in the breast and endometrium

• Increased formation of reactive oxygen species

• Stimulation of atherosclerosis and the development of metabolic syndrome

If the pineal gland is the body’s sundial, then it is obvious that any changes in the length of daylight should significantly affect its functions and, ultimately, the rate of aging. And indeed: in a number of works it was shown that violation of photoperiodicity can lead to a significant decrease in life expectancy.

American researchers M. Hard and M. Ralph discovered that golden hamsters with a special mutation in the gene responsible for generating rhythmic signals in the suprachiasmatic nucleus of the hypothalamus (namely, these signals set the melatonin production rhythm) was 20% lower than in the control group of animals. This effect was completely eliminated by implanting hypothalamic embryo cells of healthy hamsters into the brain of old mutant hamsters.

Experimental destruction of the suprachiasmatic nucleus also leads to a reduction in the life expectancy of animals. This is not surprising, because in these nuclei its activity is manifested by a whole set of the already mentioned “watch” genes. Impaired function of one of them (Per2) causes premature aging of mice and increases their sensitivity to the development of tumors. Mutations in another gene of the circadian rhythm (Clock) lead to the development of obesity and the metabolic syndrome, as well as to premature disturbances of the reproductive cycle in mice.

Numerous studies have shown that the administration of melatonin is able to slow down the aging process and increase the lifespan of laboratory animals (fruit flies, flatworms, mice, rats). In addition, there are publications about the ability of melatonin to increase the body’s resistance to oxidative stress and reduce the manifestations in humans of diseases such as retinal macular dystrophy, Parkinson’s disease, Alzheimer’s disease, hypertension, and diabetes mellitus associated with old age.

All of the above causes some optimism about the possible use of this hormone in medical practice. Of course, further comprehensive clinical trials of melatonin are needed, which, it seems, should significantly expand its scope in the treatment and prevention of age-related diseases and, ultimately, premature aging.

Literature

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