Epitalon

Description of Epithalon

Epithalon is a short synthetic tetrapeptide (Ala-Glu-Asp-Gly) with a chemical structure that is being investigated as a potential activator of the telomerase enzyme and stimulant of melatonin release. Telomerase, also known as terminal transferase, is a ribonucleoprotein adding a species-dependent telomere repeat sequence to the 3´end of telomeres. Epithalon was first discovered in late 1980s by Prof. Vladimir Khavinson from the Sankt Petersburg University, Russia. In particular studies it extended the life of mice and rats and delayed age-related degenerative changes in both the immune and reproductive systems. In addition, the peptide has shown significant effects in DNA regulation, infectious diseases, and even some types of cancer and tumorigenesis. It is suggested that antioxidative properties of epithalamin lead to increased lifespan of different researched animal species.

Research Confirmed Effects

1. Epithalon and Anti-Aging Effects

Part of the anti-aging effect of Epithalon is hidden behind the ability of pineal extract epithalamin to eliminate free radicals that damage tissues. Research in fruit flies, mice and rats has yielded interesting results regarding increased lifespan. By 52% reduction in mortality rate of fruit flies and rats after epithalamin administration, and by 27% reduction in mortality rate of mice, compared to controls, was followed. The study showed that epithalamin stimulates synthesis and secretion of melatonin in rats and inhibits free radical production in rats and fruit flies. These antioxidative properties seem to enhance lifespan of the three kinds of animals mentioned above.

In addition, experiments on human somatic non-reproductive cells in vitro suggested that Epithalon peptide induces telomerase activity – expression of the catalytical subunit, enzymatic activity and telomere elongation. Prolonging lifespan of the cells could have been due to reactivation of telomerase gene in somatic cells.

In addition, experiments on human somatic non-reproductive cells in vitro suggested that Epithalon peptide induces telomerase activity – expression of the catalytical subunit, enzymatic activity and telomere elongation. Prolonging lifespan of the cells could have been due to reactivation of telomerase gene in somatic cells.

Telomeres are regions of repetitive DNA sequences at the ends of chromosomes that protect DNA health from damages. Epithalon supports the body, and there is a theory that it is Epithalon that protects DNA from damages. This process of accumulating DNA errors eventually leads to cell aging and dysfunction, or sometimes even to cancer. Furthermore, the peptide lowers the level of chromosomal instability in patients with hypertrophic cardiomyopathy (HCM), a hereditary disease that affects the heart muscle, and their relatives. On the basis of identified protective action of Epithalon, it could be used as prevention for patients with risk of morbidity HCM.

Studies also showed that treatment of mice with Epithalon slowed down the age-related switching-off of estrous function and decreased the frequency of chromosome aberrations in bone marrow cells.

2. Epithalon and DNA Activation

However, understanding the profound effects of the Epithalon peptide on longevity and prolonging lifespan requires further scientific investigation. Except of its antioxidant effects or the effects on telomeres, it seems that the peptide also changes the expression of certain genes. As cell research has shown, Epithalon interacts directly with DNA with the promoter regions of CD5, IL-2, MMP2 and Tram1 genes and increases their expression. Whereas CD5 and IL-2 influence immune system functions and MMP2 is important in maintaining the extracellular matrix in skin, tendons and other connective tissue, and Tram1 increases protein production. Based on this, it can be concluded that the peptide affects immune response, but also the body's ability to heal itself.

The decrease of lymphocyte interferon gamma expression during aging is one of the main mechanisms leading to the immunodeficiency. The effect on the immune system proven by research on rats showed that Epithalon increases the expression of interferon gamma, a critical signaling molecule in the immune system, in aging lymphocytes. Through this immune activation in T cells, interferon gamma is essential in the fight against infections. The geroprotective peptide has the capability to activate the proliferation of lymphocytes in thymus during aging.

3. Epithalon and Skin Cell Regeneration

The actual goal of gerontocosmetology is to find new effective and harmless low- molecular substances as the short tetrapeptide Epithalon could also be like. Interaction with Epithalon leads to the activation of several genes, including the gene MMP2 found also in the skin that regulates this protein, as well as the activation of fibroblasts producing and maintaining MMP2. Even other components such as collagen and elastin are activated. However, the influence of Epithalon on organotypic skin cell cultures proliferation in young and old animals were also investigated.

Young and old rats exposed to Epithalon had stimulated skin fibroblast proliferation by 29-45%. It is therefore clear that the peptide helps by activating fibroblasts to increase the speed of skin healing and to compensate for the processes in the structure and integrity of the skin that occur during aging.

Another effect of Epithalon on the skin fibroblasts during aging is the reduction of the enzyme caspase-3 activity, which is in the pathway of apoptosis or programmed cell death. Epithalon inhibits MMP-9 synthesis increased during aging of skin cells and enhances the expression of proteins Ki-67 and CD98hc that, on the other hand, need stimulation during aging.

4. Epithalon and Tumorigenensis

Daily administration of Ephitalon to rats with cancer was investigated due to tumor growth and effect on lifespan in different illumination regimes. One group was constantly illuminated and the other was exposed just to natural light conditions. In conclusion of this experiment the peptide exhibited virtually no effect on the development of spontaneous tumors in rats exposed to standard and constant illumination, but significantly inhibited their development in rats exposed to natural light.

The peptide reduces not only tumor growth, but also delivery and spread to distant tissues. This means it has antimetastatic effect as was showed in the research of spontaneous tumorigenesis in female mice mostly with tumors of the reproductive organs as mammary glands and ovaries. With Epithalon injections 5 times a week the number of tumors was decreased and also prevented the development of metastases. Actually, no metastases were found in the experimental mice, and long-term administration of Epithalon in small doses did not show any toxic effect.

Epithalon is currently being researched as a potential drug for Her-2/neu positive breast cancer and in preventing the development of certain types of leukemia and testicular cancer. Epithalon not only decelerates aging, it also suppresses development of breast adenocarcinomas in transgenic Her-2/neu mice. Experimental mice got injections of the peptide 5 times a week, and the results showed that it suppressed the formation of neoplasms, decreased lungs metastases by 1,6 times, multiple tumors by 2 times, 3,7-fol increase of mice without breast tumors and decrease of mice with 6 or more tumors by 3 times. Epithalon injected to rats exposed to any photoregimen also significantly inhibited the development of spontaneous tumors, primarily testicular leydigomas and leukemias.

The circadian gene PER1 is a protein that helps regulate the circadian rhythm and is usually overexpressed in cancer patients. However, there is already evidence that Epithalon activates gene for this protein. PER1 affects cancer growth and causes an increased rate of ionizing radiation-induced cell death, but it is unclear whether its lack of expression precedes and contributes to cancer development, or is the only source of cancer. Controlling PER1 expression could be one way to naturally slow of tumor growth. Research shows that overexpression of PER1 sensitizes human cancer cells to the effects of DNA damage-induced apoptosis. It could therefore help also to reduce the necessary doses of radiation in the treatment of certain types of cancer, reduce side effects and the occurrence of secondary tumors appearing during treatment.

Finally, PER1 levels were reduced in human cancer patients. Results therefore highlight the importance of circadian regulation to fundamental cellular functions and support the hypothesis that disruption of core clock genes may lead to cancer development.

5. Melatonin Secretion and Epithalon Influence

The hormone melatonin, produced in the pineal gland, is associated also with sleep and aging. As found in research in rats, regulatory peptides such as Epithalon affect gene transcription, its synthesis and release. This is done by stimulating the expression of two vitally important proteins, arylalkylamine-N-acetyltransferase (AANAT) and the transcriptional protein pCREB. Both play an essential role not only in the production of melatonin, but also in the circadian control of its release during the day and night. Epithalon binds promoter regions of retinal genes F379, telomerase, and RNA polymerase II. As indicated by research in monkeys, Epithalon restores melatonin production to normal rates. Due to disorders in pineal gland in elderly age in monkeys and humans, too, melatonin release decreases. Epithalon recovers night release of endogenous melatonin and leads to the normalization of the hormone circadian rhythm in the blood plasma.

6. Epithalon on Eyesight

Epithalon appears to help maintain and improve the normal structure of the eye retina condition while increasing the bioelectric and functional activity of the retina due to the preservation of its morphological structure. A research study in rats suffering from retinitis pigmentosa demonstrated that the peptide improved results in 90% of cases. The analysis of Epithalon effects suggests that the tetrapeptide participates in the mechanisms of transcription common for the epiphysis and retina and can be beneficial in positive clinical effects.

📚 Academic References & Citations

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