Nanopep

“NANOPEP” the new and only Sheet Face Mask with Epitalon

from Khavinson Peptides
Scientifically proven correction of age-related skin changes.

Stimulates the metabolic processes in the skin cells and accelererats its regeneration. Restores skin freshness and elasticity. Prevents its premature aging

  • Restores skin natural regeneration
  • Activates skin vitality and radiance
  • Strengthens skin elasticity and collagen structure
  • Inhibits process of skin aging due to a strong antioxidant effect
  • Increases the length of telomeres (https://en.wikipedia.org/wiki/Telomere)

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Aging is a Consequence of Cellular Disease

Aging

New way of thinking : It’s a Result of Cellular Disease

Futurism.com has issued a new article about aging, and addresses new ways of thinking. Sure enough. For instance, how can treat meningitis if you wait for it to damage half the brain ? Medicine needs to act proactivily. In this regard, Bio Regulators have already moved to this new revolution.

A long record of peptide bioregulators application in the health service  has demonstrated their high effectiveness in combating various disease and pathologies, including those refractory to other medicines.

The researchers developed a new technology for creating biologically active food supplements (parapharmaceuticals), based on peptide complexes isolated from animal organs and tissues. A new group of parapharmaceuticals has received a name of “Cytomaxes”. Biologically active food supplements are produced in the form of tablets and capsules. Cytomaxes exert a regulatory effect on the cellular level and are used for improving the organism resistance to the impact of adverse environmental, climatic, occupational and other factors, as well as during the rehabilitation period after surgeries, traumas, diseases; in case of malnutrition, high physical loads; for the purpose of maintaining the functions of the main organism systems in old and very old persons in order to reduce the risk of disease occurrence.

Bio Regulators for:

Digestive system: Svetinorm, Suprefort, Stamakort or Ovagen, Vesugen, Crystagen

Vascular system: Ventfort, Svetinorm, Vladonix or Vesugen, Crystagen

Cardiovascular system: Chelokhart, Ventfort, Svetinorm

Central nervous system: Cerluten, Ventfort, Svetinorm or Pinealon, Vesugen, Ovagen

Immune system: Vladonix, Endoluten, Ventfort or Crystagen, Vesugen, Ovagen

Locomotor apparatus: Sigumir, Ventfort, Vladonix or Cartalax, Vesugen, Crystagen

Carbohydrate metabolism: Suprefort, Endoluten, Ventfort

Respiratory system: Honluten, Crystagen, Vesugen

Lipoprotein metabolism: Svetinorm, Suprefort, Ventfort

Thyroid gland: Thyreogen, Ventfort

Vision: Visoluten, Cerluten, Ventfort

Kidneys: Pielotax, Ventfort

After radio and chemotherapy, psycho-emotional stress and similar adverse factors:

Vladonix, Svetinorm, Endoluten or Vesugen, Ovagen, Honluten

 

Entdeckung der Bio Regulatoren

Entdeckung der Bio Regulation

Es ist bekannt, dass die spezifische Grenze der tierischen und menschlichen Lebensdauer um ungefähr 30-40% höher liegt als ihre mittlere Lebensdauer. Es konnte auf die Auswirkung von unerwünschten Faktoren zurückgeführt werden, die Veränderungen in der Genstruktur und der Expression hervorrufen, begleitet von Störungen in der Proteinsynthese und Organismusfunktion (Abb. 1).

Fig. 1. Potenzielle Zunahme der durchschnittlichen menschlichen Lebenserwartung bis zur spezifischen Grenze (biologische Reserve).

Zu Beginn der 1970er Jahre untersuchten wir den Mechanismus der Immundepression sowohl experimentell als auch klinisch. Wir fanden heraus, dass mit dem Altern eine Involution des zentralen Organ des Immunsystems – Thymus (Abb. 2, 3) und der des neuroendokrinen Systems – Zirbeldrüse stattfindet. Wir haben auch eine deutliche Abnahme der Proteinsynthese in Zellen verschiedener Organismusgewebe registriert (Abb. 4).

Subkapsulärer Kortexbereich (offene Biopsie, ein 2-jähriges Kind).
A – Hämatoxylin- und Eosinfärbung;
B – thymische Poly-Bioreaktoren Fluoreszenz in den Körpern und Prozessen von Epithelzellen, die Klark-Alveolen bilden, sowie Granulate auf den Thymozytenmembranen in den Alveolen.

Subkapsulärer Kortexbereich (Schnittbiopsie, ein 46-jähriger Mann).
A – Hämatoxylin- und Eosinfärbung;
B – thymische Poly-Bio-Regulator-Fluoreszenz in den Körpern und Prozessen von Epithelzellen, die Gruppen von 2-5 Zellen bilden. 2. Altersbedingte Involution von Thymus (indirektes Immunfluoreszenzverfahren mit Antikörpern gegen thymische Poly-Bioreaktoren, x600).

 

 

 

 

 

Groups
(age)
Optic density
(у.е.)
Area of expression
(%)
1
(0.5 – 4 years)
2.05±0.06 3.36±1.54
2
(65 – 79 years)
0.54±0.02* 1.24±0.06*
3
(80 – 95 years)
0.39±0.01* 0.99±0.03*
* р < 0.05 as compared to Group 1

 

Immuno fluorescence laser confocal microscopy, х400 (red fluorescence – Rodamin G, green fluorescence – FITC).

Fig. 3. Expression of transcription proteins (PAX 1) in human thymus epithelial cells (the study was conducted in cooperation with Prince Philippe Biomedical Research Center, Valencia, Spain).

Fig. 4. Protein synthesis in hepatocytes of rats of different age.

To restore functions of thymus, pineal gland and other organs we developed a special method for isolation, refinement and fractionating of low-molecular bio regulators from extracts of these organs [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][12, 13]. Low-molecular bio regulators isolated from thymus (preparation Thymalin) and pineal gland (preparation Epithalamin) of animals were studied in different biologic models. These bio regulator preparations contributed to a reliable increase in animals mean lifespan in numerous experiments (Fig. 5) [12, 13, 14, 15, 16, 17]. Of particular importance is a correlation between mean lifespan and the main index of cellular immunity (reaction of blast-transformation of lymphocytes with phytohaemagglutinin) determining T lymphocytes function (Fig. 6) [14].

Fig. 5. The increase in the average lifespan up to the specific limit after bio regulator preparations application (mean results after 15 experiments).

Fig. 6. Bio regulator preparations effect on mean lifespan and reaction of blast-transformation of lymphocytes with phytohaemagglutinin in mice.

A significant increase in the mean lifespan of animals was evidently caused by a reliable antitumoral activity (Fig. 7) of low-molecular bio regulators isolated from thymus and pineal gland [14, 15, 17, 18, 19].

Fig. 7. Effect of pineal gland preparation on the frequency of tumor incidence in animals.

Small bio regulators isolated from different organs and tissues as well as their synthesized analogues (di-, tri-, tetrapeptides) revealed a realiable tissue specific (gene specific) effects both in cellular cultures and in experimental in young and old animals (Fig. 8).

Fig. 8. Bio regulator tissue-specific (gene-specific) regulation.

Bio regulator tissue specific activity manifested in stimulation of protein synthesis in cells of those organs they had been isolated from. The enhancement of protein synthesis under the effect of bio regulator has been registered in young and old animals (Fig. 9).

Fig. 9. Effect of the liver and pineal bio regulator preparations on protein synthesis intensity in hepatocyte monolayer culture in rats of different age.

Especially significant appeared restoration of reproductive function system in old female rats subjected to the pineal bio regulator treatment (Fig. 10) [13]. Estrus phase in animals, analogous to menopause in women, lowered from the initial 95% down to 52% after the preparation administration, while other phases of the cycle, typical of the normal estrus, increased from the initial 5% up to 48%. It should be emphasized that in a special experiment initially none of the rats got pregnant after mating. Repeated mating after the administration of the pineal gland bio regulator entailed pregnancy in 4 out of 16 animals which gave birth to 5-9 healthy off-springs each.

Fig. 10. Effect of bio regulator preparation of the pineal gland on constant estrus in old female rats.

Thus there were ascertained main advantages of low-molecular bio regulators: they possessed high biologic activity, revealed tissue specificity and were neither species specific nor immunogenic. These features make regulatory bio regulators similar to bio regulator hormones [16, 20, 21].

A detailed study of molecular weight, chemical properties, amino acid composition and sequence of low-molecular bio regulators isolated from thymus, pineal gland and other organs had been carried out for many years [22, 23, 24, 25, 26]. The obtained data were used for chemical synthesis of several small bio regulators. A comparative analysis showed that biological activity of natural and synthetic preparations was largely identical. Thus, for example, thymus dipeptide stimulated immunity [24, 25]. Biological activity of natural and synthetic bio regulators appeared to be similar in standard testing in tissue cultures and in animals [27, 28, 29, 30]. These results demonstrate prospects for application of these bio regulators as geroprotectors [31, 32, 33]. The necessity of searching for new drugs – geroprotectors dictated the onset of preclinical studies of these preparations on different structural levels.

On the level of the organism in different animals we have registered a significant variety of biologic effects exerted by small bio regulators especially by bio regulators of thymus and pineal gland, including proliferative activity and apoptosis [34, 35, 36, 37, 38, 39, 40, 41, 42].

On the level of cellular structures, small bio regulators activate heterochromatine in the cell nuclei in senile patients (Table 1) [11, 43].[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Bio Regulatoren

BIO REGULATOREN

Eine unglaubliche praktische Lösung um das menschliche Leben zu VERLÄNGERN

Altern und die Proteinsynthese
Altern ist ein wichtiger Risikofaktor für Krankheit und Tod, aber was ist die Ursache des Alterns? Trotz vieler Theorien ist es noch unbekannt. Was wir wissen ist, dass wenn wir älter werden, unser Körper weniger Proteine produziert, die eine große Anzahl von wichtigen Funktionen in unserem Körper haben. Beispielsweise:

Proteine sind lebenswichtig für die Zellteilung, die für das Wachstum, der Fortpflanzung und Heilung erforderlich sind. Viele Proteine sorgen dafuer das alles richtig funktioniert, dies wird durch chemische Reaktionen reguliert. Beispiele fuer Enzyme, Hormone, Blutgerinnungs Substanzen, auch Rezeptoren in den Augen.
Protein ist wichtig für das Immunsystem um sich gegen fremde Eindringlinge zu verteidigen, wie Bakterien und Viren. Proteine helfen dem Körper andere Nährstoffe zu transportieren, sie zu binden und los zu lassen, wann und wo sie gebraucht werden. Protein helfen den richtigen Flüssigkeitshaushalt zu regulieren und zu pflegen. Diese helfen fuer den richtigen Blutdruck und sogar um die Augen feucht zu halten. Bestimmte Proteine haben eine wichtige strukturelle Rolle in den Geweben, wie Muskeln und Haut und bieten auch die Matrix für Knochen und Zähne. Im Grunde genommen stellt unser Körper tausende von spezifischen Proteinen her, die eine wichtige Rolle im täglichen functioning- dienen. Der menschliche Körper besteht etwa zu 45%  aus Protein als Trockensubstanz.

Die Alterung ist mit dem Rückgang der Synthese von Protein verbunden, so kann man logisch annehmen, dass wenn die Synthese wieder hergestellt werden kann, das man das Altern verlangsamt. Da es diese Annahme richtig ist, stellte sich heraus. Wissenschaftler haben einen Weg zum reparieren der Protein-Produktion gefunden und haben unglaubliche Ergebnisse erzielt. Die folgenden Methoden, können die Lebensdauer zwischen 20 und bis zu 40% verlängern.

Auslösende Moleküle

Die Informationen über die verschiedene Proteine sind in der DNA gespeichert. Um eine Proteinsynthese auszulösen, muss ein DNA Fragment, ein Gen aktiviert werden, das das auslösen von Molekülen mit Peptiden aktiviert. Peptide sind relativ kurze Ketten von Aminosäuren, die einen wesentlichen Teil der Zelle mit selbstregulierendem Mechanismus darstellen:
Die Zellen bauen ständig alte Proteinen ab, die sie in Aminosäuren und Peptide spalten. Einige dieser Peptide passen in bestimmte Teile der Zell-DNA. Als Ergebnis nimmt das Peptid die Synthese des Proteins, von dem es ursprünglich gebaut war wieder auf. Wenn das Protein altert, wird es wieder in die gleichen Peptide fragmentiert. All dies bildet einen Kreislauf, der einen entscheidenden Einfluss auf die Lebensdauer der Zellen hat.

Da wir mehr den negativen Umwelteinfluessen und Stress ausgesetzt sind, ist in den Zellen der selbst regulierenden Mechanismus beeinträchtigt und wir leiden dann an einem Peptid Mangel. Peptid-Mangel führt zu Zellfehlfunktionen und schließlich zu Krankheiten und vorzeitiger Hautalterung. Glücklicherweise kann man den Peptid-Protein-Zyklus mit Bio Regulatoren wiederherzustellen.

Peptide wurden aus fast allen Körpersystemen extrahiert und zeigten erstaunliche gewebespezifischen Eigenschaften, das heißt, sie haben positive Auswirkungen auf die Organe, aus denen sie extrahiert wurden.
In den letzten 40 Jahren wurden diese Bio Regualtoren von mehr als 15 Millionen Menschen genommen und keine Nebenwirkungen festgestellt. Tatsache ist, dass Peptide evolutionär den selbstregulierende Zellen Mechanismus haben und deren Struktur ist relativ einfach, sie haben keine baulichen Veränderungen im Laufe der Zeit unterzogen. Das bedeutet, dass Peptide, in Tieren und Menschen identisch sind. Außerdem ist es auch bewiesen, dass die Aufnahme von Peptiden nur die Proteinsynthese normalisieren kann und es nicht eine Zelle ueberstimuliert da eine Zelle nicht mehr Peptide aufnehmen kann, als sie es braucht.

Bio Regulator supplements
Für viele Jahre waren die Peptidpräparate nur als Arzneimittel in Form von Injektionen zu haben. Jetzt haben wir
Nahrungsergänzungsmittel (Bio Regulatoren), die ebenfalls den Peptid-Mangel reduzieren und den Peptid-Protein-Zyklus in den Zellen wiederherstellt. Diese gibt es als natürliche und synthetische Bio Regulatoren.

Natural Bio Regulators
Die natürlichen Peptide sind eine Gruppe von Peptiden mit weniger als 50 Aminosäuren und mit einer Molekülmasse von weniger als 5 kDa, frei von Fremd-DNA oder Proteinsubstanz, extrahiert aus Organen und Geweben von jungen Kälbern durch ein patentiertes Verfahren zur gründlichen Filterung. 5 kDa ist sehr wenig. Die Molekularmasse von DNA-Fragmenten und proteinöse infektiöse Partikel, die Prionen, sind mehrfach größer als das. Daher sind diese Bio Regulatoren extrem reine Produkte. Sie haben keine immunogene oder mutagene Eigenschaften.
Im Inneren des Magen-Darm-Trakt teilen sich die natürlichen Peptide in Aminosäuren und Di-, Tri- und Tetrapeptide auf, die der DNA in einer komplementären Weise entsprechen um die Proteinsynthese in den jeweiligen Körpersystemen zu aktivieren. Ihre Leistung ist sanft und allmählich. Ihre Wirkung wächst weiter auch wenn der Einnahme Zyclus beendet wurde und hält an bis zu 4-6 Monate, bis der Peptid-Protein-Zyklus wieder beeinträchtigt wird.

Warum sollte ich Bio Regulators anwenden ?

Warum sollte ich Bio Regulators anwenden ?

ZUR STÄRKUNG DES IMMUN SYSTEMES –                                       EIN ZUVERLÄSSIGER SCHUTZ IHRER GESUNDHEIT!

– Bekommen Sie oft eine Erkältung?
– Sind Sie ständig unter Stress?
– Lebst Sie in einer Gross Stadt?
– Rauchen Sie?

Wenn Sie mit „Ja“ auf mindestens zwei Fragen beantwortet haben – ist Ihr
Immunsystem ist in Gefahr! Die Immunität verringert die Toleranz des Organismus gegenüber schädlichen Faktoren des äußeren und inneren Umfelds, was einer der Gründe für die Entwicklung von Krankheiten und die beschleunigte Alterung ist.

Die Verwendung von Bio-Regulatoren verbessert die Arbeit des Immunsystems und fördert die Wiederherstellung der Reservefähigkeit des Organismus aufgrund ihrer hohen Immunmodulatoraktivität.

EIN AUSGEGLICHENER STOFFWECHSEL – IST DIE BESTE GARANTIE FUER IHRE GESUNDHEIT!

Jedes Mal, wenn wir über Gesundheit zu sprechen, sprechen wir über den Stoffwechsel – ein Faktor, der entscheidend für unseren Körper ist.
Der Stoffwechsel ist der Prozess, durch den unser Organismus Stoffe, die in Lebensmitteln enthalten sind, in Energie oder Baustoff für unsere Organe verwandelt.
Proteine spielen eine der wichtigsten Rollen bei der Erhaltung des Stoffwechsels in unserem Körper. Abnahme der Proteinsynthese mit dem Alter führt zu Fehlfunktionen der Austauschprozesse.
Das Auftreten von Krankheiten hängt davon ab, welches Organ die Zeichen einer gestörten metabolischen Funktionen aufweist. So, wenn es im Knochengewebe vorkommt – kann Osteoporose entstehen, in der Bauchspeicheldrüse – Diabetes, in der Leber – Pankreatitis, etc.
Die Anwendung der Bio-Regulatoren stimuliert die Wiederherstellung des Ungleichgewichts in Organen und Geweben.

Bio Regulation of Aging

Bio Regulation of Aging

Discovery of bio regulation regulation of ageing

It is known that specific limit of animal and human lifespan is approximately 30-40% higher than their mean lifespan. It could be referred to the impact of adverse factors causing changes in the gene structure and expression accompanied by disorders in the protein synthesis and organism functioning (Fig. 1).

Fig. 1. Potential increase in the average human lifespan up to the specific limit (biological reserve).

At the beginning of the 1970ies we studied the mechanism of immunodepression both experimentally and clinically. We found out that with ageing there takes place an involution of the central organ of immune system – thymus (Fig. 2, 3) and that of the neuroendocrine system – pineal gland. We also registered definite decrease of protein synthesis in cells of different organism tissues (Fig. 4).

Subcapsular cortex area (open biopsy, a 2-year old child).
A – hematoxylin and eosin staining;
B – thymic poly bio regulators fluorescence in the bodies and processes of epithelial cells forming Klark’s alveoli, as well as granules on the thymocyte membranes inside alveoli.

 

 

 

Subcapsular cortex area (section biopsy, a 46-year old man).
A – hematoxylin and eosin staining;
B – thymic poly bio regulators fluorescence in the bodies and processes of epithelial cells forming groups of 2-5 cells.Fig. 2. Age-related involution of thymus (indirect immunofluorescent method with antibodies to thymic poly bio regulators, x600).

 

 

Groups
(age)
Optic density
(у.е.)
Area of expression
(%)
1
(0.5 – 4 years)
2.05±0.06 3.36±1.54
2
(65 – 79 years)
0.54±0.02* 1.24±0.06*
3
(80 – 95 years)
0.39±0.01* 0.99±0.03*
* р < 0.05 as compared to Group 1

Immuno fluorescence laser confocal microscopy, х400 (red fluorescence – Rodamin G, green fluorescence – FITC).

Fig. 3. Expression of transcription proteins (PAX 1) in human thymus epithelial cells (the study was conducted in cooperation with Prince Philippe Biomedical Research Center, Valencia, Spain).

Fig. 4. Protein synthesis in hepatocytes of rats of different age.

To restore functions of thymus, pineal gland and other organs we developed a special method for isolation, refinement and fractionating of low-molecular bio regulators from extracts of these organs [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][12, 13]. Low-molecular bio regulators isolated from thymus (preparation Thymalin) and pineal gland (preparation Epithalamin) of animals were studied in different biologic models. These bio regulator preparations contributed to a reliable increase in animals mean lifespan in numerous experiments (Fig. 5) [12, 13, 14, 15, 16, 17]. Of particular importance is a correlation between mean lifespan and the main index of cellular immunity (reaction of blast-transformation of lymphocytes with phytohaemagglutinin) determining T lymphocytes function (Fig. 6) [14].

Fig. 5. The increase in the average lifespan up to the specific limit after bio regulator preparations application (mean results after 15 experiments).

Fig. 6. Bio regulator preparations effect on mean lifespan and reaction of blast-transformation of lymphocytes with phytohaemagglutinin in mice.

A significant increase in the mean lifespan of animals was evidently caused by a reliable antitumoral activity (Fig. 7) of low-molecular bio regulators isolated from thymus and pineal gland [14, 15, 17, 18, 19].

Fig. 7. Effect of pineal gland preparation on the frequency of tumor incidence in animals.

Small bio regulators isolated from different organs and tissues as well as their synthesized analogues (di-, tri-, tetrapeptides) revealed a realiable tissue specific (gene specific) effects both in cellular cultures and in experimental in young and old animals (Fig. 8).

Fig. 8. Bio regulator tissue-specific (gene-specific) regulation.

Bio regulator tissue specific activity manifested in stimulation of protein synthesis in cells of those organs they had been isolated from. The enhancement of protein synthesis under the effect of bio regulator has been registered in young and old animals (Fig. 9).

Fig. 9. Effect of the liver and pineal bio regulator preparations on protein synthesis intensity in hepatocyte monolayer culture in rats of different age.

Especially significant appeared restoration of reproductive function system in old female rats subjected to the pineal bio regulator treatment (Fig. 10) [13]. Estrus phase in animals, analogous to menopause in women, lowered from the initial 95% down to 52% after the preparation administration, while other phases of the cycle, typical of the normal estrus, increased from the initial 5% up to 48%. It should be emphasized that in a special experiment initially none of the rats got pregnant after mating. Repeated mating after the administration of the pineal gland bio regulator entailed pregnancy in 4 out of 16 animals which gave birth to 5-9 healthy off-springs each.

Fig. 10. Effect of bio regulator preparation of the pineal gland on constant estrus in old female rats.

Thus there were ascertained main advantages of low-molecular bio regulators: they possessed high biologic activity, revealed tissue specificity and were neither species specific nor immunogenic. These features make regulatory bio regulators similar to bio regulator hormones [16, 20, 21].

A detailed study of molecular weight, chemical properties, amino acid composition and sequence of low-molecular bio regulators isolated from thymus, pineal gland and other organs had been carried out for many years [22, 23, 24, 25, 26]. The obtained data were used for chemical synthesis of several small bio regulators. A comparative analysis showed that biological activity of natural and synthetic preparations was largely identical. Thus, for example, thymus dipeptide stimulated immunity [24, 25]. Biological activity of natural and synthetic bio regulators appeared to be similar in standard testing in tissue cultures and in animals [27, 28, 29, 30]. These results demonstrate prospects for application of these bio regulators as geroprotectors [31, 32, 33]. The necessity of searching for new drugs – geroprotectors dictated the onset of preclinical studies of these preparations on different structural levels.

On the level of the organism in different animals we have registered a significant variety of biologic effects exerted by small bio regulators especially by bio regulators of thymus and pineal gland, including proliferative activity and apoptosis [34, 35, 36, 37, 38, 39, 40, 41, 42].

On the level of cellular structures, small bio regulators activate heterochromatine in the cell nuclei in senile patients (Table 1) [11, 43].

Table 1

Effect of bio regulators on chromatin in lymphocytes of old humans 

Bio regulators Associating acrocentric chromosomes (per cell) Deheterochroma-tinization of optional heterochromatin (per cell) Total hetero-chromatin Structural heterochromatin of the 1st chromosome
Control
(20-40 years old)
1.33±0.06 7.7±0.4 Stable state Stable state
Control
(75-88 years old)
1.17±0.05* 5.9±0.2* Heterochroma-tinization Heterochroma-tinization
Dipeptide
Lys-Glu
2.39±0.11** 9.9±0.6** Deheterochroma-tinization Heterochroma-tinization
Tetrapeptide
Ala-Glu-Asp-Gly
2.32±0.12** 8.4±0.5** Deheterochroma-tinization Deheterochroma-tinization

* p<0.05 compared to the control (20-40 years old)
** p<0.001 compared to the control (75-88 years old)

As it was said above there are two forms of chromatin in the cellular nucleus: light euchromatin and dense heterochromatin located near nuclear membrane. Gene transcription takes place in the light phase, that’s in euchromatin. With ageing the amount of heterochromatin in the nucleus increases on average from 63% to 80%. Regulatory bio regulators entail the increase in the amount of euchromatin in the nucleus. This means that more genes become available for transcription factors, and transcription of gene information goes on more intensively as well as protein synthesis. In other words the more euchromatin there is in the nucleus the more intensive the protein synthesis in the cell is [10, 11, 43].

The capability of bio regulators to induce polypotential cells differentiation is of special significance (Fig. 11) [42]. Thus addition of retinal bio regulators to polypotential cells of Xenopus laevis early gastrula ectoderm led to the emergence of retinal and pigment epithelium cells. This outstanding result explains a pronounced clinical effect of the preparation of the retina in patients with retinal degenerations [42] and in animals with genetically determined retinitis pigmentosa.

Fig. 11. Induction effect of retinal bio regulators on the polypotent cells of Xenopus laevis early gastrula ectoderm.

On a chromosome level the number of chromosomes aberrations was used a marker of DNA damages in an ageing organism. Somatic mutations can occur due to accumulation of stable aberrations and underlie age-related pathology, including malignant neoplasia. Reliable antimutagenic and reparative activity of thymus and pineal gland bio regulators have been confirmed by a reduction in the number of chromosome aberrations in the bone marrow cells and cornea epithelium cells in animals revealing accelerated ageing [45].

On the level of gene activity regulation it was established that administration of bio regulators Lys-Glu and Ala-Glu-Asp-Gly to transgenic mice caused a 2–3.6-fold suppression of HER-2/neu gene expression (human breast cancer) as compared to the control group. This suppression is accompanied by a reliable reduction of the tumor diameter (Fig. 12) [41].

Fig. 12. Bio regulators effect on the development of mammary adenocarcinoma and HER-2/neu oncogene expression in transgenic mice (the study was conducted in cooperation with the National Research Centre on Ageing, Ancona, Italy).

It was revealed that addition of tetrapeptide Ala-Glu-Asp-Gly to the cultural medium of human lung fibroblasts induces telomerase gene expression and contributes to a 2.4-fold lengthening of telomeres. Activation of gene expression is accompanied by a growing number of cellular divisions (by 42.5%), which is the evidence of Hayflick’s limit overcoming (Fig. 13) [46, 47].

The effect of di- and tetrapeptides Lys-Glu, Glu-Trp, Ala-Glu-Asp-Gly, Ala-Glu-Asp-Pro on the expression of 15 247 murine heart and brain genes before and after bio regulators administration was studied with the employment of DNA-microarray technology [48]. In this experiment, there were used clones from the library of the National Institute on Ageing, USA. This experiment provided unique data on alteration in the expression of different genes under the effect of bio regulator preparations (Fig. 11). An important conclusion driven from the experiment was that every bio regulator specifically regulates particular genes. Results of this experiment testify to the existing mechanism of bio regulator regulation of gene activity. It was also registered that dipeptide Lys-Glu, showing immunomodulating activity, regulates gene interleukin-2 expression in blood lymphocytes [49].

Fig. 13. Overcoming human somatic cell division limit due to introduction of the bio regulator into the culture of the pulmonic fibroblasts.

Fig. 14. Bio regulator effect on gene expression in the heart of mice (the study was conducted in cooperation with the National Institute on Aging, Baltimore, USA).

On the molecular level, there was an obvious gap between multiple evidence of specific effects, caused by regulatory bio regulators in activation of gene transcription [50, 51, 52, 53, 54, 55, 56, 57, 58], and limited schemes of the process underlying the selective binding of the transcription factor with specific DNA sites. Meanwhile non-specific binding of proteins with the DNA double helix was proved using physicochemical methods [59]. Activation of gene transcription in cells of higher organisms as a rule needs dozens of macromolecular activators and transcription factors.

We proposed a molecular model of interaction between regulatory bio regulators and DNA double helix in gene promoter region of (Fig. 15, 16, 17, 18) [60, 61].

Fig. 15. Unfolded bio regulator Ala-Glu-Asp-Gly conformation (plan projection). There are shown end and side functional groups, capable of complementary interaction with DNA.
—NH3 – proton donors groups;
=O – proton acceptors groups;
—CH3 – hydrophobic (methyl) group.
Bold line – main bio regulator chain.

Fig. 16. Metric location of functional groups exposed onto the surface of the DNA major groove in case of embedding of each nucleotide pair into DNA double helix. Dash line – perpendicular plane, where aromatic structures of nucleic bases are located.
—NH2 – proton donors groups;
=7N – proton acceptors groups;
—CH3 – hydrophobic (methyl) group.
Fig. 17. Sequence of nucleotide pairs in the DNA double helix, functional groups of which are complimentary to functional groups of Ala-Glu-Asp-Gly bio regulator. This sequence is many times repeated on the promoter segment of telomerase gene.Fig. 18. Scheme of complementary interaction of tetrapeptide Ala-Glu-Asp-Gly with DNA double helix (“DNA-tetrapeptide” complex on the promoter segment of telomerase gene).

Geometrical and chemical complementarity of bio regulator amino acid sequence and DNA nucleotide pairs sequence was assumed as a basis for the molecular model. Regulatory bio regulator recognizes a specific site in the DNA double helix if its own amino acid sequence is complementary to the DNA nucleotide sequence for a sufficient length. In other words their interaction is specific due to matching sequences.

Each sequence of the DNA double helix nucleotide pairs forms a unique pattern of functional groups on the surface of the DNA double helix major groove. A bio regulator in the unfolded β-conformation can complimentary fit into the in the DNA major groove along the double helix axis. We used data on molecular geometry of the DNA double-helix and bio regulator β-thread from scientific publications in order to identify nucleotide pairs sequence for specific binding of the DNA and bio regulator Ala-Glu-Asp-Gly. The screening conducted showed that this tetrapeptide can be located in the DNA major groove with the ATTTG (or ATTTC) nucleotide sequence on the main chain in compliance with the complementarity of disposition of their functional groups [59].

For experimental testing of the molecular model there were used synthetic preparations: DNA [poly(dA-dT):poly(dA-dT)] (double helix) and tetrapeptide Ala-Glu-Asp-Gly. Gel chromatography helped to prove that bio regulator Ala-Glu-Asp-Gly forms stable intermolecular complex with the DNA double helix (Fig. 19) [61].

1 – individual Ala-Glu-Asp-Gly bio regulator
2 – free DNA double helix [poly (dA-dT) : poly (dA-dT)]
3 – mixture of bio regulator and DNA

Fig. 19. HPLC of bio regulator and DNA on sefadex G-25 in physiological solution at room temperature.

Complementary binding of the bio regulator with nucleotides sequence on the leading strand TATATA of the double helix can be conducted by six hydrogenous and one hydrophobic bonds between functional groups of the both participants.

Under normal physiological conditions DNA exists in the form of a double helix two polymeric chains of which are kept together by hydrogenous bindings between pairs of bases of each chain. Most of the biological processes with DNA participation (transcription, replications) need the double helix to undergo disjunction into separate strands. In particular, it is known, that local separation of double helix strands precedes gene transcription by RNA polymerase. For the transcription onset (synthesis of the matrix RNA) the DNA double helix has to be freed from histones, and in the place where the matrix RNA synthesis starts, the strands of the double helix should be disintegrated (Fig. 20).

Fig. 20. The scheme of local separation of strands [poly (dA-dT) : poly (dA-dT)] as a result of bio regulator Ala-Glu-Asp-Gly binding in DNA double helix major groove.

Concentration dependent hyperchromic effect (increased optic density 260 nm) was found by spectrophotometery of solutions containing synthetic DNA double helix and tetrapeptide Ala-Glu-Asp-Gly. The hyperchromic effect points out a partial destruction of hydrogen bonds between nucleotide pairs of the double helix and local separation of its strands (allosteric conformational changes) [61].

It was experimentally revealed that detachment (melting) of free DNA strands occurs at the temperature +69.50С. In the “DNA-tetrapeptide” system melting of the double helix occurred at the temperature +28°С and was characterized by approximately 2-fold decrease in the values of entropy and enthalpy. This fact points out a thermodynamically simplified way of the DNA strands separation in temperature settings typical of biochemical processes of the majority of living organisms. In vitro experiments show that a small bio regulator of the definite structure and amino acid sequence can participate in activation of genes transcription on the stage of strands disjunction in the DNA double helix. Biochemical aspect of this phenomenon consists in similarity of structure and amino acid sequence of a regulatory bio regulator and a specific segment of the bio regulator chain of the macromolecular transcription factor.

Thus, the studies of bio regulators biological activity on different structural levels and of physicochemical processes of their interaction proved an indubitably high physiologic activity of bio regulator regulators. Major conclusion reads that bio regulators are capable of regulating gene expression. Pre-clinical trials demonstrated high biological activity and safety of synthesized bio regulators [61, 63, 64, 65]. Thus, the administration of bio regulators Lys-Glu, Ala-Glu-Asp-Gly to animals contributes to a reduced incidence of tumors and an increase of mean lifespan [66, 67, 68]. Bio regulator Ala-Glu-Asp-Pro stimulates nerve regeneration [69], bio regulator Lys-Glu-Asp-Trp decreases blood glucose level in animals with experimental diabetes mellitus [70].

Taking into consideration a reliable biological activity of bio regulators we found it reasonable to study the effect of regulatory bio regulators in monkeys. Restoration of the melatonin level up to normal following the administration of the bio regulator preparation to old monkeys was among our significant achievements.

Fig. 21. The bio regulator effect on melatonin production in monkeys of different age.

The same old monkeys revealed a restoration to normal indices of a daily rhythm of secretion of the main hormone of adrenal gland – cortisol (Fig. 22).

Fig. 22. The bio regulator effect on cortisol production in monkeys of different age (in the morning and in the evening).

Taking into consideration the encouraging data testifying to high geroprotective activity of both natural tissue specific and synthetic bio regulator preparations we have been concentrating our attention on studies of geroprotective activity of bio regulators in old and senile people in recent years [42, 57, 71, 72, 73, 74, 75, 76]. Thus, annual treatment course with thymus and pineal preparations led to a reliable decrease in mortality (Table 2), due to improvement of brain function and that of immune, endocrine, cardio-vascular systems, increased density of osseous tissue (Fig. 23, 24) [42, 57, 71, 72]. It is noteworthy that application of preparation of the thymus led to a 2-fold decrease in frequency of acute respiratory disease (Fig. 25) [57]. The restoration of melatonin secretion level in patients subjected to administration of preparation of the pineal gland is of special significance (Fig. 26) [71, 71]. These results suggest good prospects for tackling demographic issues [77].

Table 2

bio regulator preparation effect on mortality rate in elderly and old patients

Group of patients

Indices

Control (administration of polyvitamins)

Administration of the pineal gland preparation

Administration of the complex of thymus and pineal gland preparations

Elderly people
(60-74 years)

Initial mean age, years

69.3 ± 2.2

71.1 ± 1.4

No studies

Mortality rate in the course
of 8 years, %

13.6

8.5*

Mortality rate in the
course of 12 years, %

44.1

22.3*

Old people
(75-89 years)

Initial mean age, years

80.2 ± 1.6

81.5 ± 2.1

82.1 ± 2.3

Mortality rate in the course of 6 years, %

81.8

45.8*

33.3*

* p<0.05 compared to the control

Fig. 23. Effect of thymus preparation on metabolism in elderly patients (60-74 y.o.).

Fig. 24. Dynamics of reaction of blast-transformation of lymphocytes with phytohaemagglutinin index in elderly patients in 3 years after 6 courses of bio regulator preparations.

Fig. 25. ARD incidence in elderly and old people treated with thymus preparation.

Fig. 26. Effect of the pineal gland preparation on melatonin level in elderly people.

Conclusion

The mechanisms of ageing studies showed that an involution of the main organs and tissues of the organism accompanied by a decrease of protein synthesis in cells underlies the process of ageing.

Bio regulator preparations isolated from organs of young animals when introduced into an old organism are capable of inducing protein synthesis, followed by restoration of the main functions.

It was registered that long-term application of bio regulators, both isolated from the organs and synthesized from the amino acid, in animals (as a rule starting from the second half of their life) leads to a reliable increase in their mean lifespan by 20-40% and reaching a specific limit.

It was revealed that small bio regulators (di-, tri- and tetrapeptides) are capable of complementary interaction with the DNA specific binding site on the promoter segment of genes, inducing disjoining of double helix strands and RNA polymerase activation. Discovery of the phenomenon of bio regulator activation of gene transcription points out the natural mechanism of organism to maintain physiologic functions, which is based on the complementary interaction of the DNA and regulatory bio regulators. This process is fundamental for the development and functioning of the living substance (Fig. 27, 28), while ageing is an evolutionary determined biologic process of age-related changes in gene structure and expression.

Application of bio regulators in humans for preventive purposes led to a significant rehabilitation of the main physiological functions and a reliable mortality decrease in different age groups during the period of 6-12 years.

Fig. 27. The role of bio regulators in the cycle of DNA, RNA and protein biosynthesis.

Fig. 28. Mechanism of bio regulator regulation of the living matter development.

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Bio Regulators

BIO REGULATORS

AN INCREDIBLE PRACTICAL SOLUTION TO PROLONG HUMAN LIFE

Aging and protein synthesis

Aging is a major risk factor for disease and death but what is the cause of aging? Despite many theories it is still unknown. What we know is that as we age our body produces fewer proteins that have a large number of important functions in our body. For example:

  • Proteins are vital to cell division, which is necessary for growth, reproduction and healing.
  • Many proteins keep everything working right by regulating chemical reactions. Examples include enzymes, hormones, blood clotting substances, even receptors in the eyes.
  • Protein is essential for the immune system to defend against foreign invaders such as bacteria and viruses.
  • Proteins help to transport other nutrients around the body by binding to them and then releasing them when and where they are needed.
  • Protein helps to regulate and maintain a proper fluid balance. This helps to maintain proper blood pressure and even lubricate eyes.
  • Certain proteins serve a major structural role in tissues such as muscle and skin and even provide the matrix for bones and teeth.

Basically, our bodies make thousands of specific proteins that serve important roles in everyday functioning— in fact, the human body is about 45% protein on a dry matter basis.

Triggering molecules

The information about different proteins is stored in the DNA. In order to launch protein synthesis a DNA fragment, a gene, has to be activated by triggering molecules, bio regulators. Bio regulators are relatively short chains of amino acids and they are an essential part of the cell self-regulating mechanism:

Cells constantly degrade aged proteins by breaking them down into amino acids and bio regulators. Some of these bio regulators match specific parts in the cell DNA following the lock-key principle. As a result, the bio regulator resumes the synthesis of the protein from which it was originally built. When the protein ages, it is fragmented into the same bio regulators once again. All of this forms a circular process that is vital to cell life.

biosynthesis_small_315b5799-fcdd-4d43-aa4f-88e5967225b8_grande 

However, due to extended exposure to environmental hazards and stress this cell self-regulating mechanism is compromised and we become bio regulator deficient. bio regulator deficiency leads to cell malfunction and eventually to diseases and premature aging. Luckily, we can restore the bio regulator-protein cycle with bio regulator supplements.

Conclusion

There is still no way to stop aging but thanks to the scientists’ intensive work during the last 40 years, we finally have dietary supplements that substantially slow down aging by reducing bio regulator deficiency and restoring cell bio regulator-protein cycles in the body. Thus, if you want to live longer being mentally and physically healthy you have now a real solution.

Why should I use Bio Regulators ?

Why should I use Bio Regulators ?

STRONG IMMUNITY – RELIABLE PROTECTION OF YOUR HEALTH!

– Do you often catch cold?
– Are you constantly under a stress?
– Do you live in a big city?
– Do you smoke?

If you answered “yes” to at least two of the questions – your
immunity is in danger! Dis-immunity reduces organism’s tolerance to harmful factors of the external and the internal environment which is one of the reasons for the development of diseases and accelerated aging.

The use of Bio Regulators improves the work of the immune system and promotes the restoration of reserve capabilities of the organism due to their high immun modulator activity.

WELL BALANCED METABOLISM – THE BEST GUARANTEE OF YOUR HEALTH!

Each time when we come to talk about health, we speak about metabolism – a factor which is crucial for our body.
However not everyone knows what it is and most importantly – what it does for us.
Metabolism is the process by means of which our organism transforms substances contained in food into energy or the building material for our organs.
Proteins play one of the most important roles in maintaining metabolism in our bodies. Decrease of protein synthesis with age, leads to malfunctions of the exchange processes.
Occurrence of diseases depends on what organ shows the signs of a disrupted metabolic functions. So, if it occurs in the bone tissue – osteoporosis can take place, if in the pancreas – diabetes, in the liver – pancreatitis, etc.
Application of the Bio Regulators stimulates restoration of the disbalance within organs and tissues.