Effect of glycative stress on sleep

Yoshikatsu YUNEI, Director of the Research Center for Glycative Stress, Doshisha University (Japan)

Masayuki Yagi, Anti-ageing Medicine Research Center, Glycative Stress Research Center, Graduate School of Life and Medical Sciences, Doshisha University (Japan)

Wakako TAKABE, Anti-ageing Medicine Research Center, Glycative Stress Research Center, Graduate School of Life and Medical Sciences, Doshisha University (Japan)

Upon detailed study, it turned out that glycative stress provokes destructive processes in the body, participates in the pathogenesis of diseases caused by metabolic disorders, and accelerates aging

The aging of the body is accompanied by a large number of different processes and symptoms. Aging of blood vessels, bones, muscles and nerve fibers causes, respectively, atherosclerosis, osteoporosis, sarcopenia and Alzheimer's disease. In addition, there are many risk factors associated with the onset of aging that appear and progress gradually in people in their 30s and 40s and can often lead to disease.

However, a collection of symptoms is called a disease only when a diagnosis is made based on diagnostic criteria.

It is much better if it is possible to detect symptoms as early as possible - in 30-40 years , in order to delay their progression and prevent the onset of the disease, than to begin treatment after diagnosis. Medical institutions practicing anti-age therapy recommend conducting examinations to assess the degree of aging of the body and associated risk factors. The degree of severity of the aging process is reflected in the functional age of the vascular, nervous, hormonal, muscular and skeletal systems.

Risk factors consist of indicators of psychological, oxidative, glycation, immune stress and a person’s lifestyle

For example, smoking causes oxidative and glycative stress , which, accordingly, leads to the development of atherosclerosis and diabetes mellitus, as well as lipid metabolism disorders. If weaknesses in the body develop with age, without proper treatment, this can lead to subsequent functional impairment. The most serious risks cascade intensify the others. While strengthening weak points and eliminating the most significant risk factor creates the necessary balance of health .

GLYCATIVE STRESS

Glycation stress is a pathological condition associated with excessive production of reduced sugars (glucose), lipids and various aldehydes. The aldehyde reacts with biological substances, forming carbonyl groups of proteins and/or advanced glycation end products (AGEs) . Activation of receptors for AGE (RAGE) triggers various processes that lead to diseases and destructive changes associated with aging.

Causes of glycative stress:

• surges in blood glucose levels;
• lipid metabolism disorders, such as high levels of triglycerides and low-density lipoproteins;
• excessive alcohol consumption

Each of these factors provokes the formation of aldehyde. A person's fasting blood glucose level may be within normal limits, but after a meal it can jump to 7.8 mmol/L or higher. Recent studies have found that postprandial hyperglycemia causes rapid progression of atherosclerosis and other pathological conditions.

A spike in glucose levels causes an “aldehyde spark,” which triggers the formation of different types of aldehydes down the chain: glyceraldehyde (GA), glycolaldehyde, acetaldehyde (AA), 3-deoxyglucose (3DG), glyoxal (GO), methylglyoxal (MGO), and malondialdehyde.

Aldehyde group (-CHO) are highly reactive compounds whose formation is controlled by substrate concentration, temperature and time, and does not require any participation in the enzyme reaction

During surges in glucose levels, cyclic saccharides circulate in the blood. During glycation, part of the glucose molecule is decyclized to an open linear form. The aldehyde group (-CHO) opens up and has a negative effect on cells. However, the rate of the ring opening reaction (i.e. the transition to the linear form) is only 0.002%, the adverse effect called glucotoxicity is reduced. Thus, we hypothesized that surges in glucose levels produce various aldehydes in a chain reaction. The open aldehyde backbone in the linear form of glucose reacts with carbohydrate chains on the surface of proteins or free sugars (glucose, fructose, pentose) in the blood and tissue fluid.

Recently, there has been debate about the connection between surges in glucose levels and damage to the vascular endothelium, which leads to an increased risk of cardiovascular disease.

However, the reason for this relationship remains unclear. “Aldehyde spark” reactions certainly play an important role in the pathogenesis of endothelial tissue damage, since aldehydes react very actively with protein. We should not interpret glucose spikes as physiological postprandial hyperglycemia.

GLYCATIVE STRESS AND DISEASES ASSOCIATED WITH AGING

The antioxidant defense system of the human body has successfully coped with oxidative stress for several hundred thousand years. However, several decades ago, glycative stress already became a threat to the entire population of the planet. This was partly due to changes in our diet and decreased physical activity.

The human body is extremely vulnerable to glycative stress. The number of diseases associated with it is increasing in the population - obesity, diabetes mellitus and dyslipidemia.

Advanced glycation end products (AGEs) are captured by cell surface scavenger receptors, which are responsible for disposing of metabolic waste products such as denatured protein. This leads to the fact that the endoplasmic reticulum, which takes part in the synthesis and transport of proteins, lipids and hormones, is in a state of chronic stress, which leads to cell depletion. AGEs bind to the RAGE receptor (AGE receptor) on the surface of cells, and the cells produce TNF-α, IL-1, IL-6 and MCP-1 cytokines, which cause an inflammatory response in surrounding tissues. Glycation of skin collagen fibers leads to excessive skin tension and the appearance of a yellowish tint. Glycation of bone collagen increases the risk of fractures. There is a pathogenetic link between Alzheimer's disease and glycation of β-amyloid peptide in brain tissue, which causes inflammation in peripheral brain cells and the development of symptoms of the disease. Glycation of crystallin, which makes up the lens, causes cataracts. Glycation processes in male and female gonads can provoke infertility. These examples are only a small part of the devastating changes caused by glycative stress, which is involved in the development of diseases associated with aging.

SLEEP QUALITY AND GLYCATIVE STRESS

Approximately 40% of patients with diabetes mellitus, the pathogenesis of which also involves glycative stress, experience complications associated with sleep disorders. Obstructive sleep apnea , which is a major disorder leading to decreased sleep quality, is often associated with obesity and diabetes.

That is, there is a bidirectional correlation between sleep and carbohydrate metabolism

To reduce glycative stress, prevention and treatment of carbohydrate metabolism disorders and sleep disorders should be carried out in parallel. Previous studies have shown that the skin autofluorescence (AF) index (a technique that allows you to assess the content of oxidative and glycative stress products in the skin. - Ed. ) depends on the duration of sleep and therefore can be used as a marker of glycative stress. The diagram of the distribution of AF levels depending on age shows that the value of skin autofluorescence, and therefore the content of oxidative and glycative stress products in it, increases in people with shorter sleep duration compared to people who sleep longer.

People with sufficient sleep duration experienced decreased levels of glycative stress.

To determine the effect of sleep quality on fluctuations in blood glucose levels, we observed several volunteers. When the subjects got enough sleep, their blood glucose levels after breakfast rose slightly the next morning. However, when a person slept only 3-4 hours, after breakfast we recorded a sharp jump in blood glucose.

EFFECTS OF MELATONIN

One of the reasons that sleep quality declines with age is a decrease in melatonin synthesis in the body . Melatonin is a pineal gland hormone that plays an important role in regulating circadian rhythms.

Melatonin has powerful antioxidant effects, and recent studies have shown that it has an effect on reducing glycative stress.

In vitro studies of melatonin have shown that it does not inhibit the formation of AGEs and does not affect the interaction of AGEs with RAGE receptors. However, it turned out that melatonin fights AGEs through the cleavage of α-diketone in their composition.

Postprandial changes in glucose levels after breakfast were leveled out when melatonin was taken before bed the night before the study.

It was noted that adequate sleep, during which a sufficient amount of melatonin is synthesized, helps to avoid surges in blood glucose levels

Melatonin affects carbohydrate metabolism as follows:

• reduces the secretion of glucocorticoids in the adrenal cortex (cortisol);
• restores the functioning of orexins in the brain (they also affect metabolic processes. – Editor’s note );
• reduces stress of the endoplasmic reticulum of pancreatic β-cells and restores insulin secretion.

COMBAT GLYCATIVE STRESS AND IMPROVE SLEEP QUALITY

The list of steps to reduce glycative stress can be divided into four groups according to the four stages of the glycation reaction:

• slow down the absorption of carbohydrates and fats - substances that cause glycative stress;
• prevent the formation of advanced glycation end products;
• stimulate the elimination of advanced glycation end products;
• control the functioning of RAGE receptors.

To slow down the absorption of fats and carbohydrates, it is recommended to eat slowly, chew food thoroughly, start with high-fiber vegetables, and drink yogurt before meals.

It is not recommended to eat white rice and freshly baked bread. To suppress the formation of glycation products, it is important to drink liquids rich in antiglycative ingredients - green tea, rooibos, chamomile tea and eat a variety of vegetables and fruits.

Insufficient and inadequate sleep contributes to visceral obesity and metabolic disorders of fats and carbohydrates

You can see that improving sleep quality plays a critical role in counteracting glycative stress . It is necessary to improve sleep conditions (remove sound and light stimuli), start taking melatonin and learn recovery techniques after physical and psychological stress. As our research has shown, a comfortable orthopedic bed not only ensures sound sleep, but also improves the metabolism of carbohydrates and lipids.

Melatonin has antioxidant and antiglycative effects, promotes the degradation of advanced glycation end products and improves the metabolism of carbohydrates and lipids. Melatonin secretion decreases with age, causing sleep disturbances such as difficulty falling asleep, night awakenings and very early morning awakenings.

Therefore, we recommend that people suffering from metabolic disorders, which are accompanied by a decrease in sleep quality, arrange a comfortable sleeping place, start drug treatment for obstructive apnea syndrome and take melatonin.

CONCLUSIONS

Sleep quality and glycative stress, which accelerate and aggravate the processes associated with aging, influence each other. Decreased sleep quality causes spikes in blood glucose levels, and then an “aldehyde spark” that triggers a cascade of aldehyde formation. Further research is required for a deeper study of the pathogenetic mechanisms of decreased sleep quality and ways to combat it as a factor influencing the progression of diabetes mellitus and age-related changes associated with glycative stress.

This research was supported by JSPS KAKENHI Grant No. 17K01880. The results were presented at the XVI World Congress on Anti-Aging Medicine in Monte Carlo (Monaco).

First published in "Les Nouvelles Esthétiques Ukraine" No. 1 (113) 2019