NUTRIGENOMIC ORTHOMOLECULAR COMPOSITION (OYOX) AND ITS ROLE IN ACTIVATION OF SIRTUINE SERIES PROTEINS. ANTI-AGING EFFECTS

Abstract: Aging develops against the background of a deficiency of sirtuin-type proteins. The anti-aging effect can be achieved mainly by replenishing the deficiency of SIRT1 proteins; SIRT3; SIRT6. The nutrigenomic orthomolecular composition OYOX plays an important role in replenishing the deficiency and activating sirtuin-type proteins. OYOX increases the amount of sirtuins and increases their functional activity. The role of the orthomolecular composition OYOX has been studied experimentally. Within a few minutes after contact with «CYC-8», which is the main active molecule of the drug, the MAPK / ERK pathway is activated, followed by an increase in the production of sirtuins of the SIRT1 genes; 3; 6 (with a maximum of 12 hours) activation reaches a maximum after 16-48 hours.

Key words: anti-aging effect, rejuvenation, prevention of aging, orthomolecular composition, nutrigenomic preparation, OYOX, sirtuin-type proteins, protein activation, SIRT1 replenishment; SIRT3; SIRT6.

ФИО, должность (на русском)

Город, учреждение (на русском)

НУТРИГЕНОМНАЯ ОРТОМОЛЕКУЛЯРНАЯ КОМПОЗИЦИЯ (OYOX) И ЕЕ РОЛЬ В АКТИВАЦИИ БЕЛКОВ СИРТУИНОВОГО РЯДА. АНТИВОЗРАСТНЫЕ ЭФФЕКТЫ

Аннотация: Старение развивается на фоне дефицита белков сиртуинового типа. Антивозрастного эффекта можно достичь преимущественно за счет восполнения дефицита белков SIRT1; SIRT3; SIRT6. Важная роль в восполнении дефицита и активации белков сиртуинового типа отводится нутригеномной ортомолекулярной композиции OYOX.

Препарат OYOX увеличивает количество сиртуинов, повышает их функциональную активность. Роль ортомолекулярной композиции OYOX была изучена в эксперименте. В течение нескольких минут после контакта с «CYC-8», которая является основной действующей молекулой препарата, происходит активация MAPK/ERK пути с последующим увеличением производства сиртуинов генов SIRT1; 3; 6 (с максимумом 12 ч.) активации достигает максимума через 16-48 часов. Побочных эффектов отмечено не было.

Ключевые слова: антивозрастной эффект, омоложение, предотвращение старения, ортомолекулярная композиция, нутригеномный препарат, OYOX, белки сиртуинового типа, активация белков, восполнение SIRT1; SIRT3; SIRT6.

Aging is a process of gradual suppression of the basic functions of the body (regenerative, reproductive, etc.), as a result of which the body loses its ability to maintain homeostasis, withstand stress, disease and injury. The loss of functions makes age-related pathologies inevitable, which are the causes of death. Aging is traditionally viewed as mechanical wear and error accumulation. In this model, random errors and stress caused by environmental factors lead to metabolic disruption, increased production of free radicals and damage to macromolecules in every cell and tissue. There is evidence that environmental changes in the biological component of mortality (that is, aging) also depend on the activity of certain genes, cytokines and hormones, which means it can be corrected and regulated. An important role in the regulation of aging mechanisms is played by proteins of the sirtuin type, in particular, proteins SIRT1, SIRT3, SIRT6 [1].

The relationship between sirtuin proteins and aging processes. The role of sirtuin proteins in maintaining aging mechanisms has been studied experimentally. Yeast cells are widely used as an experimental model. It was shown that with increased expression of proteins encoded by the Sir2 gene, an increased ability of cells to divide is observed. At the same time, a characteristic feature is the regulation of division processes through epigenetic mechanisms, that is, division processes require a lower degree of chromatin condensation. However, no direct involvement in repairing DNA damage has been observed. It was also shown in experimental models that similar processes are characteristic of all mammals, including humans. However, in humans, similar functions are performed by the SIRT1 protein, which is a functional analogue of the yeast Sir2 gene [4]. Sirtuins are directly related to the processes of cellular aging. Aging is based on the gradual loss of sirtuin proteins of their function associated with the regulation of cell division processes. The mechanism of cellular aging is associated with two main processes [3].

The essence of the first process is that sirtuins deacetylate histones at lysine residues. As a result, chromatin condensation occurs, as a result of which the production of those proteins and genes that are not needed by the cells at a given time is turned off, and even have a negative effect. This allows you to maintain the functional state of the cell and prevents premature aging. Turning off such regulatory mechanisms leads to disruption of the processes of cell division, products of protein synthesis and gene expression accumulate, which have a negative effect on the cell. As a result, cellular aging, cell death occurs [5].

The second regulatory mechanism is aimed at preventing DNA damage. Normally, sirtuin-type proteins are immediately localized at the site of DNA damage and provide repair processes, as a result of which DNA is restored. As a result, the damaged genes are reactivated, their inclusion in regulatory and metabolic processes. However, when the function of sirtuins is impaired, when they are deficient, the rate of repair processes decreases, a large amount of damaged DNA accumulates in the cell, which leads to aging and cell death [6].

In the human body, proteins of the sirtuin series perform both functions. This ensures homeostasis — the stability of the internal environment. However, with age, one of the functions is gradually lost. In most cases, the amount of free radicals increases, and therefore intense DNA damage occurs. Accordingly, sirtuin proteins are switched to provide repair processes. In this case, gene activation occurs, sometimes excessive. Other proteins, the activation of which is not needed by the cell, can also undergo repair processes. Excessive gene activation leads to premature cellular senescence [2].

Sirtuins act in several ways [7]:

— proteins of the sirtuin type inhibit the transcriptional activity of the p53 gene, which acts as a tumor suppressor, triggering the processes of apoptosis. As a result of apoptosis, the cell dies, and its uncontrolled multiplication, and, accordingly, tumor growth, is impossible. With a deficiency of sirtuin-type proteins, in particular, SIRT1, the activity of this gene decreases sharply, as a result of which the ability to apoptosis decreases, and, accordingly, the risk of malignant cell transformation increases, and tumor growth occurs.

— Ku70, deacetylated by SIRT1 and SIRT3, binds the pro-apoptotic mitochondrial factor Bax, which inhibits apoptosis.

— Poly (ADP-ribose) -polymerase (PARP) uses NAD +, which gradually leads to cell death; SIRT1 deacetylates and inhibits PARP.

— Deacetylation of HSF1, a transcription factor that protects cells from heat shock and misfolded proteins, plays an important role in the survival of cells under heat shock conditions. SIRT1 deacetylates HSF1, increasing its affinity for DNA.

— SIRT1 deacetylates the FOXO transcription factors, thereby inducing stress-resistant proteins, which leads to the fact that the cell cycle is suspended and the number of reactive oxygen species decreases.

Anti-aging effect of sirtuin-type proteins. Aging develops against the background of a deficiency of sirtuin-type proteins. Deficiency of proteins of the sirtuin type negatively affects both the state of individual metabolic processes and the state of the body as a whole. Accordingly, when replenishing the deficiency of sirtuin-type proteins, it is possible to achieve an anti-aging effect, to slow down the aging process. The anti-aging effect can be achieved by replenishing the deficiency of SIRT1 proteins [12].

The optimal content of proteins of this type increases the rate of cell division, increases the rate of epigenetic mechanisms, which is reflected in the acceleration of repair processes, an increase in the rate of damage healing, and an increase in tissue regeneration. The body’s ability to turn off inactive genes and repair DNA damage is significantly increased. At the same time, the amount of free radicals decreases, which reduces, and often completely prevents, the risk of oxidative stress, prevents premature aging and cell death. The normal content of this type of protein significantly increases the transcriptional activity of the tumor suppressor p53, as a result of which the processes of cell apoptosis are normalized and tumor growth is prevented [8].

When the deficiency of this type of protein is replenished, the protein’s ability to deacetylate HSF1 increases, as a result of which the risk of cell death from heat shock is reduced, and the accumulation of incorrectly folded proteins in the cell space is prevented. The number of stress-resistant proteins increases, as a result of which the cell cycle accelerates, and the number of reactive oxygen species also increases significantly. This reduces the risk of oxidative stress and prevents premature cellular aging. Also, by eliminating the protein deficiency, it is possible to normalize the concentration of glucose in the blood, in connection with which the risk of developing diabetes mellitus and metabolic disorders decreases [10].

The normal content of SIRT3 proteins prevents disruption of the neural network and the signaling cascade, normalizes the course of metabolic processes in the neuroglia, as a result of which the risk of developing neurodegenerative diseases and Alzheimer’s disease decreases. Also, the ratio of AMP / ATP in cells is normalized, as a result of which all processes of oxidative phosphorylation are normalized, and the rate of ATP synthesis is increased. Accordingly, the energy potential of the cell increases, metabolic processes are normalized. At normal protein content, the regulators of the tricarboxylic acid cycle are activated, and oxygen metabolism is normalized [11].

Replenishment of the deficiency of SIRT6 proteins leads to a normalization of the immune response, as a result of which the risk of developing infectious diseases decreases, the risk of malignant cell transformation, the likelihood of developing oxidative stress decreases, which prevents the risk of premature aging. In addition, the normal content of this type of protein normalizes lipid metabolism, reduces the risk of developing atherosclerosis, metabolic disorders [8].

Nutrigenomic orthomolecular composition OYOX and its role in replenishing the deficiency and activation of sirtuin-type proteins. OYOX is an innovative dietary supplements created by German scientists from the pharmaceutical company Danda Pharma. It represents a new generation of physiologically active compounds that return the body to a youthful regimen. OYOX contains components that activate the production of sirtuins.

These complex proteins perform the function of controllers in the body, culling damaged cells and giving the command to replace them with young ones. Age-related decline in sirtuin levels is one of the main causes of aging. OYOX increases the amount of sirtuins. This activates the production of neurotransmitters (serotonin, dopamine, acetylcholine, endorphins, etc.), as well as collagen, enzymes, hormones (estrogen, testosterone) [9].

OYOX contains a complex of bioactive components, many of which have been used in oriental medicine for centuries, for example [9]:

— Cycloastragenol — an extract of astragalus membranous («herb of life»), well known in Chinese medicine. It has an adapotogenic, immunomodulatory effect, increases physical endurance, reduces reactions to stress, stimulates the synthesis of sirtuins, and has an antioxidant effect.

— Phosphatidylserine — a natural lipid, accelerates the processes of cellular metabolism and cell renewal, accelerates and activates the synthesis of neurotransmitters. — Resveratrol — a natural antioxidant, immunomodulator, reduces the level of «bad» cholesterol, helps detoxify the body.

— L-theanine — improves the nutrition of the brain, improves the quality of sleep, the ability to remember.

— Selexen — a source of selenium, improves falling asleep (the production of melatonin — sleep hormone), facilitates morning awakening, normalizes the hypothalamus, balanced work of all organs and body systems.

— Griffonia extract — increases the production of serotonin.

The role of the orthomolecular composition OYOX has been studied experimentally.

In the course of the experiment, the isolated PBMC cells and CD8 T-lymphocytes from patients aged 30-92 years were exposed to the dietary supplements based on the CYC-8 molecule. 72 hours after the initial stimulation, the sirtuin activity in the samples was measured. As a second stimulation, this process was repeated after 18 days. The following results were obtained:

1. “The CYC-8 stimulated effect of enhancing the activity of sirtuins in PBMCs of donors aged 30-35 years was relatively moderate, ranging from 1.5 to 2.5 times. «CYC-8» significantly increased the activity of sirtuins in PBMCs in the 36-55 age group from 3.5 to 7 times. In the age group 57-87 years, the activity of sirtuins increased from 2.5 times to 14 times.
2. Within a few minutes after contact with «CYC-8», activation of the MAPK / ERK pathway occurs, followed by an increase in the production of sirtuins of the SIRT1 genes; 3; 6 (with a maximum of 12 hours) activation reaches a maximum after 16-48 hours.
3. Short 7 days exposure to «CYC-8» on CD4 + CD8 + T-lymphocytes resulted in a small but statistically significant increase in the number of population doublings compared to untreated control cells.
4. As a result of this work, no evidence was obtained that the use of «CYC-8» contributed to the loss of growth control and transformation in the culture of the studied cells. Moreover, «CYC-8» does not lead to any significant increase in the constitutive activity of sirtuins in the healthy young age group 22-28 years old.
5. An increase in the cytobiochemical marker of the number and activity of mitochondria in peripheral blood lymphocytes was found, which confirms the realization of increased activity of sirtuins 1, 3,6 at the level of mitochondriogenesis.

Conclusion

Sirtuins are a family of evolutionarily conserved NAD-dependent proteins with deacetylase or ADP-ribosyltransferase activity. Traditionally, it is customary to consider sirtuins in close connection with the processes of aging, cell death, immune response, and metabolic reactions. Deficiency of proteins of the sirtuin type negatively affects both the state of individual metabolic processes and the state of the body as a whole. Proteins SIRT1, SIRT3, SIRT6 are closely interconnected and their mechanism of action is largely intertwined. Aging develops against the background of a deficiency of sirtuin-type proteins.

Deficiency of proteins of the sirtuin type negatively affects both the state of individual metabolic processes and the state of the body as a whole. Accordingly, by replenishing the deficiency of sirtuin-type proteins, it is possible to achieve an anti-aging effect, slowing down the aging process. The anti-aging effect can be achieved mainly by replenishing the deficiency of SIRT1 proteins; SIRT3; SIRT6. The nutrigenomic orthomolecular composition OYOX plays an important role in replenishing the deficiency and activating sirtuin-type proteins. The core of the OYOX composition is the key complex molecule «CYC-8» containing cycloastragenol «CYC-8».

The drug OYOX increases the amount of sirtuins and increases their functional activity. The role of the orthomolecular composition OYOX has been studied experimentally. Within a few minutes after contact with «CYC-8», which is the main active molecule of the drug, the MAPK / ERK pathway is activated, followed by an increase in the production of sirtuins of the SIRT1 genes; 3; 6 (with a maximum of 12 hours) activation reaches a maximum after 16-48 hours.

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