What Is Epitalon?

“In 1973 the first evidence was published that administration of the low-molecular-weight pineal peptide extract (commercial form was named later as Epithalamin) was followed by restoration of the estrus cycle in old female rats with persistent estrus syndrome and by lowering of the threshold of sensitivity of the hypothalamo-pituitary complex to feedback inhibition by estrogens in old animals. Since this work, the effect of epithalamin on the function of the reproductive, endocrine, neuroendocrine and immune systems was systematically studied in our own and our colleagues’ experiments. There was shown a high biological activity of epithalamin. Long-term treatment with the preparation prolongs the life span of animals, slows down the aging of the reproductive system, improves the parameters of immune functions and inhibited the development of spontaneous tumors induced by some chemicals or X-irradiation and transplanted tumor.” (1)

Synthetic Tetrapeptide Epitalon Restores Disturbed Neuroendocrine Regulation in Senescent Monkeys

“It is important that the melatonin concentration both in the young and senescent control monkeys at 9 p.m. exceeded that at 9 a.m. This also conforms to the evidence of increased melatonin secretion in the evening.” (2) “Melatonin content in the senescent control animals was twice less (p<0.01) than that in the young controls, especially in the evening. This corresponds to the published data on decreased melatonin content in human and animal blood in aging… We registered a significant increase in the evening-time melatonin concentration in the Epitalon-administered animals (Figure 1). For instance, it exceeded the corresponding control value in 20–26 year old Epitalon-affected monkeys (p<0.001) more than 3 times, while in the young animals Epitalon introduction did not exert any significant effect upon melatonin content in the blood.” (2) Epitalon did not significantly influence the basal production of adrenal androgens (DHEA, DHEAS), sex steroid hormones (estradiol and progesterone) and thyroxin.” (2) epitalon, Elixir Labs Co

Peptide Correction of Age-Related Pineal Disturbances in Monkeys

“Administration of pineal peptides–epithalamin (at the dose 5 mg/animal/day intramuscularly during 10 consecutive days) or epitalon (at the dose 10 micrograms/animal/day intramuscularly during 7-10 consecutive days) induced significant increase in the night plasma melatonin in old monkeys, but the treatment did not change the melatonin level in young monkeys. Taking into consideration that melatonin is very important for regulation of the diurnal rhythm of functioning of some organs and systems it should be suggested that applying epithalamin and epitalon are perspective in the correction of age-related hormonal imbalance and age pathology.” (3)

Multiple Studies Show Epitalon Helped Stabilize Circadian Rhythms

“Peptide preparations of the pineal gland (Epithalamin–a complex of peptides isolated from the pineal gland and Epitalon–synthetic tetrapeptide) recover night release of endogenous melatonin and lead to the normalization of the hormone circadian rhythm in the blood plasma. In elderly people Epithalamin and Epitalon modulate pineal gland functional state: people with pineal gland functional insufficiency report an increase of night melatonin level. The preparations of the pineal gland, effectively increasing melatonin concentration and having no side effects, can be used in clinical geriatric practice.” (4) epitalon, Elixir Labs Co

Pineal Peptide Preparation Epithalamin Increases The Lifespan of Fruit Flies, Mice and Rats

“Mortality rate was decreased by 52% in D. melanogaster, by 52% in rats, by 27% in C3H/Sn mice. It did not change in SHR mice exposed to epithalamin. Treatment with the pineal peptide increased MRDT in flies, C3H/Sn mice and rats. It has been shown that epithalamin increases synthesis and secretion of melatonin in rats and inhibits free radical processes in rats and in D. melanogaster. It is suggested that antioxidative properties of epithalamin lead to increased lifespan of three different animal species.” (5)

Effect of Epitalon on The Lifespan Increase in Drosophila Melanogaster

“Epitalon significantly increased the lifespan (LS) of imagoes by 11–16% when applied at unprecedented low concentrations — from 0.001×10–6 to 5×10–6 wt.% of culture medium for males and from 0.01×10–6 to 0.1×10–6 wt.% of culture medium for females.”

Peptide Geroprotector from the Pituitary Gland Inhibits Rapid Aging of Elderly People: Results of 15-Year Follow-Up

Over three years 39 coronary patients received, in addition to basic therapy, regular courses of epithalamin (peptide drug), while 40 coronary patients (control group) received basic therapy alone. Long-term treatment with epithalamin (6 courses over 3 years) decelerated aging of the cardiovascular system, prevented age-associated impairment of physical endurance, normalized circadian rhythm of melatonin production and carbohydrate and lipid metabolism. A significantly lower mortality in the group of patients treated with epithalamin in parallel with basic therapy also indicated a geroprotective effect of the peptide preparation from the pineal gland. (7)

Epitalon Activates Chromatin in Old Age

“The function of chromatin is to efficiently package DNA into a small volume to fit into the nucleus of a cell and protect the DNA structure and sequence. Packaging DNA into chromatin allows for mitosis and meiosis, prevents chromosome breakage and controls gene expression and DNA replication.” (8) “The obtained data demonstrate that Epitalon induces the activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin and the release of genes repressed due to the age-related condensation of euchromatic chromosome regions. CONCLUSIONS: Epitalon has shown its ability to activate chromatin by modifying heterochromatin and heterochromatinized chromosome regions in the cells of older persons.” (9)

Epithalon Peptide Induces Telomerase Activity and Telomere Elongation in Human Somatic Cells and Overcomes the Hayflick Limit

Each cell contains DNA as an instruction manual for how to divide and grow. The DNA inside of each cell is shielded by proteins called telomeres. During cellular division, a new cell must take some telomeres from its originating cell to shield the DNA of the new cell. The telomeres shorten after every cell division because the new cell can only take a portion of the telomeres from the previous cell, else the previous cell’s DNA will become completely unprotected. Once there are no left over telomeres to take, the cell stops dividing. This happens after a single cell divides and grows about 64 other cells, which is known as the Hayflick limit. This limit exists because cells without shield material are more vulnerable DNA damage. If the DNA of a cell becomes damaged, the cell will follow broken instructions. If the instructions within the DNA of the cell are damaged, then the cell may not be able to eliminate itself through the process of apoptosis like it is supposed to. “The telomere length is increased by approximately 33% in epitalon treated cells [by increasing the telomerase enzyme that strengthens telomeres].” (10) “Telomerase is a reverse transcriptase that has two distinct functions, to replicate pre-existing chromosome ends (telomeres) and to heal broken chromosomes by de novo addition of telomeric sequences directly on to non-telomeric DNA.” (11) epitalon, Elixir Labs Co “Addition of Epithalon to aging cells in culture induced elongation of telomeres to the size comparable to their length during early passages. Peptide-treated cells with elongated telomeres made 10 extra divisions (44 passages) in comparison with the control and continued dividing. Hence, Epithalon prolonged the vital cycle of normal human cells due to overcoming the Hayflick limit.” (12) epitalon, Elixir Labs Co

Epitalon Didn’t Affect Spontaneous Tumor Incidence but Slowed the Development of Leukemia in a Study.

“We also found that treatment with Epitalon did not influence total spontaneous tumor incidence, but inhibited the development of leukemia (6.0-fold), as compared with the control group.” (13)

Epitalon Reverses Hypophysectomy, Restoring Fibrinolysis and Reducing Blood Clotting in Chickens

“Neonatal hypophysectomy in chicken, as well as that in old hen has been established to entail in 1,5 months after surgery cellular and humoral immunity disturbances, pronounced hypercoagulation and fibrinolysis depression. Administration of Epitalon (Ala-Glu-Asp-Gly) to a large extent eliminates revealed shifts. This effect appeared to be stronger in neonatally hypophysectomized chicken than in old hens.” (14)

Epitalon Lowers a Type of White Blood Cells Associated with Accelerated Aging.

“The melatonin prevents age-specific decreasing blood lymphocytes level in standard photoperiod (12 h light/12 h darkness). Contrary to melatonin, epithalon significantly reduces the number of lymphocytes and increases the number of neutrophils in some age period. The leucocytes alkaline phosphatase activity was increased during aging. Constant light in compare with other light conditions promotes early increasing of alkaline phosphatase activity (at 12 months), associated with accelerated development of pathological process in organism.” (15)

Epitalon Selectively Boosts Cytokine IL-2.

“IL-2 was one of the first cytokines discovered and characterized and, based on its ability to stimulate the growth of T cells, was termed T cell growth factor (TCGF). Subsequently, it was shown that IL-2 can also support the growth and expansion of NK cells as well as other immune cells such as B cells at varying stages of development or activation. Perhaps surprisingly, it also plays a role in activation induced cell death of effector T cells. IL-2 plays a multifaceted and complex role in the generation, expansion, and maintenance of CD8 effector cells. IL-2, along with other cytokines, is required for optimal induction and differentiation of CD8 effector cells and may help determine the type of memory cells (central vs. effector) generated. Interestingly, in some situations IL-2 can convert naive CD8 cells into memory-like cells with minimal TCR signaling. Like many cytokines, IL-2 has evolved to act locally over short distances in an autocrine or paracrine fashion. Reflecting this property, IL-2 is found at very low levels in normal serum and exogenously introduced IL-2 has a very short serum half-life. Paradoxically, given its role in T cell proliferation, IL-2 gene deletion or “knock-out” experiments in mice, resulted in progressive lymphoid hyperplasia and the development of autoimmune diseases. This phenotype is now thought to be due to impaired development of regulatory T cells, which require IL-2, and are essential for maintaining the proper homeostatic balance of the immune system.” (16)

Boosts Endorphins by Inhibiting the Enzyme that Destroys Them.

“Epitalon inhibited enkephalin-degrading enzymes from human serum. The dose-inhibitory effect curves for Epitalon… IC50 equaled 500 microM, respectively.” (17)

Epitalon Stimulates Neuronal Activity.

“Recording of spontaneous neuron discharges for 10–15 min was followed by intranasal administration of epitalon solution and recording of neuron activity to 30 min after doses of 30 ng per animal. Significant activation of neuron activity was seen several minutes after dosage, with an increase (by factors of 2–2.5) in discharge frequency. In some experiments, the effect of epitalon was multiphasic. The first peak of increased neuron discharge frequency at 5–7 min was followed by peaks at 11–12 and 17–18 min. The increase in discharge frequency occurred because of an increase in the discharge frequency of neurons which were already active and the recruitment of previously silent neurons.” (18)

Sourced Studies:

Timeline of Epitalon studies, over the years: “Epithalamin | Semantic Scholar.” Www.Semanticscholar.Org, http://www.semanticscholar.org/topic/epithalamin/588850. (1) Vn, Anisimov, et al. “Twenty Years of Study on Effects of Pineal Peptide Preparation: Epithalamin in Experimental Gerontology and Oncology.” Annals of the New York Academy of Sciences, 31 May 1994, pubmed.ncbi.nlm.nih.gov/8010617/. (2) V, Khavinson, et al. “Synthetic Tetrapeptide Epitalon Restores Disturbed Neuroendocrine Regulation in Senescent Monkeys.” Neuro Endocrinology Letters, 1 Aug. 2001, pubmed.ncbi.nlm.nih.gov/11524632/ (3) Nd, Goncharova, et al. “[Peptide Correction of Age-Related Pineal Disturbances in Monkeys].” Advances in Gerontology = Uspekhi Gerontologii, 2003, www.ncbi.nlm.nih.gov/pubmed/14743609/. (4) Ov, Korkushko, et al. “[Normalizing Effect of the Pineal Gland Peptides on the Daily Melatonin Rhythm in Old Monkeys and Elderly People].” Advances in Gerontology = Uspekhi Gerontologii, 2007, www.ncbi.nlm.nih.gov/pubmed/17969590/. (5) Anisimov, Vladimir N, et al. “Pineal Peptide Preparation Epithalamin Increases the Lifespan of Fruit Flies, Mice and Rats.” Mechanisms of Ageing and Development, vol. 103, no. 2, 15 June 1998, pp. 123–132, www.sciencedirect.com/science/article/abs/pii/S0047637498000347, 10.1016/S0047-6374(98)00034-7. (6) Khavinson, V. Kh., et al. “Effect of Epitalon on the Lifespan Increase in Drosophila Melanogaster.” Mechanisms of Ageing and Development, vol. 120, no. 1, 1 Dec. 2000, pp. 141–149, www.sciencedirect.com/science/article/abs/pii/S0047637400002177, 10.1016/S0047-6374(00)00217-7. (7) Korkushko, Oleg V, et al. “Peptide Geroprotector from the Pituitary Gland Inhibits Rapid Aging of Elderly People: Results of 15-Year Follow-Up.” Undefined, 2011, www.semanticscholar.org/paper/Peptide-Geroprotector-from-the-Pituitary-Gland-of-Korkushko-Khavinson/a2196b363bfdf4bd78e75c26de83e948dddacaf2. (8) “Chromatin Accessibility and Architecture | Abcam.” Www.Abcam.Com, www.abcam.com/epigenetics/chromatin-accessibility-and-architecture. (9) VKh, Khavinson, et al. “Peptide Epitalon Activates Chromatin at the Old Age.” Neuro Endocrinology Letters, 1 Oct. 2003, pubmed.ncbi.nlm.nih.gov/14647006/. (10) VKh, Khavinson, et al. “Epithalon Peptide Induces Telomerase Activity and Telomere Elongation in Human Somatic Cells.” Bulletin of Experimental Biology and Medicine, 1 June 2003, pubmed.ncbi.nlm.nih.gov/12937682/. (11) P, Slijepcevic, and Bryant Pe. “Chromosome Healing, Telomere Capture and Mechanisms of Radiation-Induced Chromosome Breakage.” International Journal of Radiation Biology, 1 Jan. 1998, www.ncbi.nlm.nih.gov/m/pubmed/9464472. (12) VKh, Khavinson, et al. “Peptide Promotes Overcoming of the Division Limit in Human Somatic Cell.” Bulletin of Experimental Biology and Medicine, 1 May 2004, pubmed.ncbi.nlm.nih.gov/15455129/. (13) Vn, Anisimov, et al. “Effect of Epitalon on Biomarkers of Aging, Life Span and Spontaneous Tumor Incidence in Female Swiss-Derived SHR Mice.” Biogerontology, 2003, pubmed.ncbi.nlm.nih.gov/14501183/. (14) Bi, Kuznik, et al. “[Effect of Epitalon on the Immunity and Hemostasis in Hypophysectomized Chicken and Old Hens].” Advances in Gerontology = Uspekhi Gerontologii, 2004, pubmed.ncbi.nlm.nih.gov/15490730/. (15) Lb, Uzenbaeva, et al. “[The Influence of Melatonin and Epithalon on Blood Leukocyte Count and Leukocyte Alkaline Phosphatase in Rats Under Different Lighting Conditions During Ontogenesis].” Advances in Gerontology = Uspekhi Gerontologii, 2008, pubmed.ncbi.nlm.nih.gov/19432172/. (16) Skrombolas, Denise, and John G. Frelinger. “Challenges and Developing Solutions for Increasing the Benefits of IL-2 Treatment in Tumor Therapy.” Expert Review of Clinical Immunology, vol. 10, no. 2, 1 Feb. 2014, pp. 207–217, www.ncbi.nlm.nih.gov/pmc/articles/PMC4072333/, 10.1586/1744666X.2014.875856. (17) Nv, Kost, et al. “[Effect of New Peptide Bioregulators Livagen and Epitalon on Enkephalin-Degrading Enzymes in Human Serum].” Izvestiia Akademii Nauk. Seriia Biologicheskaia, 1 July 2003, pubmed.ncbi.nlm.nih.gov/12942748/. (18) Sibarov, D. A., et al. “Effects of Intranasal Administration of Epitalon on Neuron Activity in the Rat Neocortex.” Neuroscience and Behavioral Physiology, vol. 37, no. 9, Nov. 2007, pp. 889–893, 10.1007/s11055-007-0095-3.
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