Guide to Epitalon Peptide
Research has suggested that Epitalon, (also known as AEDG peptide, tetrapeptide Epitalon, Epithalon or Epithalone) may regulate the function of the brain, the pineal gland, and the eye retina. Several studies have proposed the following Epitalon benefits:
- May enhance sleep by stimulating the pineal gland, releasing more melatonin
- May stimulate the generation of telomerase, which inhibits age-related diseases
- May provide strong antioxidant properties
- May extend the workable integrity of the retina
With recent technology and ongoing advances in the scientific field, methods have been developed to synthesize complex peptide preparations from the extracts of several different tissues. One such peptide in the tissues is ‘Epithalamin,’ naturally produced in the pineal gland. Epithalamin has been found to be functional in increasing melatonin production, improving the immunological and anti-carcinogenic effects in rats and mice, and restoring reproductive function in old rodents. Similar effects of this naturally occurring peptide were observed in human studies, representing the geroprotectant activity of the peptide in human volunteers. Utilizing the recent advancements in science, a peptide similar to Epithalamin was synthesized and titled ‘Epitalon.’ Interestingly, Epitalon is derived from a naturally occurring peptide belonging to both pineal gland and eye retina, hence, Epitalon likely produces beneficial effects in both organs. (1)
Overview of Epitalon Peptide
Epitalon (aka Epithalon or Epithalone) is a synthetic tetrapeptide, also known as AEDG peptide, composed of amino acids Ala-Glu-Asp-Gly. (2) The peptide has been suggested to exhibit effects similar to Epithalamin via various modes of actions. This mechanism and further studies are further described below. The natural peptide, Epithalamin, was discovered by a Russian professor named Vladimir Khavinson, in the 1980s. During these preliminary studies (3), it was understood that the peptide might be useful in the elderly, patients with liver disorders, mental health, retinal disorders and in delaying the aging effects in men. Interestingly, it was also noted that when the peptide was administered in fetal cells that were telomerase negative, it appeared to induce catalytic effects of enzymes by a possible reactivation of telomerase. This indicated that the peptide might possibly increase the lifespan of the cells and thereby the lifespan of the whole organism. (3) Later, the synthetic peptide Epitalon was developed at the St. Petersburg Institute of Bioregulation and Gerontology in Russia. (4) Several studies have been conducted at the same institute, and it has been suggested that the peptide may play a key role in decreasing the mortality rate in humans and inhibiting the delay in the bodily developments with age. (4) Listed below are the key research areas of the peptide. Various studies have been conducted in vitro and in vivo in animals (primarily rodents) as well as in humans:
- Anti-aging effects
- Geroprotective properties (capability to protect DNA through production of telomerase)
- Melatonin production in the body
- Life span
- Anti-cancer effects
Research and Clinical Studies
Epitalon Peptide and Longevity
Studies (2) have suggested that the peptide binds with the histones – HI/6 and HI/3 – located at different sites in the human tissues, which then interact with the DNA. This binding of the peptide and the histones would lead to the increment of neurogenic differentiation of gene transcription involving markers such as Nestin, Beta Tubulin III and Doublecortin, by 1.6 to 1.8 times than usual. This neuronal differentiation and protein synthesis in retinal and human ligament stem cells may potentially lead to beneficial effects.
Epitalon Peptide and Anti-Aging
In order to understand the anti-aging effects of various synthetic peptides, studies have been widely conducted to study their effect on cell proliferation, cell regeneration and aging, cellular apoptosis, and matrix modeling. (5) It was suggested that Epitalon may inhibit the synthesis of MM-9 which usually increases with age, and increase the proliferation and cellular regeneration process, which usually decreases with age. Consequently, the peptide may induce the suppression of the aging process.
Epitalon Peptide and Fetal Studies
This study (6) was conducted to understand the proliferative effects of the peptide on human fetal fibroblastic cells. Pulmonary fibroblasts were isolated from the 24-week-old fetus, and it was observed that these fibroblasts appeared to lose their proliferative function at the 34th passage. These cells possessed extremely small telomeres sizes – smaller than what it originally was during the 10th passage. When Epitalon was administered in these otherwise aging cells, it appeared to stimulate the development of telomeres, causing them to increase and restore their normal size. As a result of this size elongation, the telomeres caused 10 extra cell divisions than usual seen in the control cells. Thus, this study suggested that Epitalon overcame the Hayflick limit and extended the normal cell cycle in human cells (6).
Epitalon Peptide and Lymphocytic Cells
In this study (7), lymphocytic cells were isolated and cultured from people aged between 76 and 80 years. The purpose of this study was to determine the effect of Epitalon on ribosomal cell activity and its impact on denaturation and polymorphism of heterochromatin. The outcome of this study, following the administration of the cell culture with Epitalon, was that the peptide appeared to induce activation of the ribosomal genes and decondensation of the heterochromatin. Consequently, it appeared to induce the release of genes that were otherwise suppressed due to the aging of the chromosomal regions. This study suggested that Epitalon might have the ability to modify the chromosome regions in the aging cells, activate chromatin, and restore cellular activities that were otherwise suppressed or delayed in geriatric patients.
Epitalon Peptide and Anti-Mutagenic Effects
In this 2011 study (8), three different mice models were used to determine the effect of the peptide on chromosomal aberrations. The three mice models were – SAMP-1 female mice with accelerated aging and wild rats SAMR-1 and SHR (both female mice). Upon administration of Epitalon, it was observed that the incidence of the chromosomal aberrations in the bone marrow of SAMP-1 mice with accelerated aging appeared to be almost 2 times higher than the other two models. When the peptide was administered at the age of 2 months in the mice, it appeared to decrease the chromosomal aberrations in all three models, the highest being in the SAMP-1 mice with accelerated aging. On co-administration with melatonin at night, given with water, there was no reported impact on the effects of the peptide. This study suggested that Epitalon may possess anti-mutagenic effects, which supports the peptide’s proposed geroprotective properties.
Epitalon Peptide and Anti-Cancer Properties
In this study (9), one-year-old female (C3H/He) mice with tumors on the reproductive organs (mammary glands and ovaries) were observed. The tumors on the mammary glands included several variants of the invasive ductal carcinogenic cells, whereas, in the ovaries, the tumors found were granulosa cell tumors. These mice, kept in standard conditions for six months, were divided into two groups – the control group and the experimental group. Epitalon was administered five times in a week. Once the study was completed, it was reported that 3 out of the 9 mice in the control group appeared to exhibit metastasis and an increase in the number of tumor cells. Meanwhile, the peptide-treated mice exhibited a decrease in the number of tumor cells. Epitalon, upon administration, appeared to inhibit the process of metastasis in the mice, preventing tumor cell cycle and growth. This study highlighted the anti-metastatic potential of the peptide, making it a possible anti-cancer agent.
Epitalon Peptide and Research in Hypophysectomized Birds
In this study (10), hypophysectomized birds, both young and old, were selected to study the effects of Epitalon peptide on the morphology of thymus gland. Hypophysectomized birds are birds in which the pituitary gland has been surgically removed. Upon administration of the peptide, it was discovered that the morphology of the thymus gland appeared to be restored in all birds, regardless of their age. The most effective results were observed on birds (mainly chickens) that underwent a neonatal hypophysectomy before the peptide administration. This study further supported the hypothesis that Epitalon may have geroprotective properties.
Epitalon Peptide and Melatonin Levels
This study (11) was carried out on both aging monkeys and human volunteers to determine the effects of Epitalon on melatonin levels. With increasing age, the melatonin levels in the body tend to decrease due to reduced secretion, which causes difficulty in sleep especially during night time. This is mainly due to the functioning of the pineal gland deteriorating with increased age and a reduction of hormone circadian rhythm amplitude. Upon administration of Epitalon, it appeared to stimulate effects similar to those caused by the natural secretion of the pineal gland. The melatonin levels in the body appeared to increase to “normal” levels, especially during the night time, which induces adequate sleep in elderly patients.
Epitalon Peptide and Retinal Cells
With the increasing age, eye sight tends to deteriorate. In this study (12), it was suggested that when Epitalon was administered in geriatric patients, it appeared to elevate the bioelectric and functional activities in the retina, thereby preserving the morphological structure of the retina. As a result, age-related retinal degeneration may be reversed in the old patients, which is supported by the positive clinical outcome in 90% of the patients treated with the peptide.
Epitalon and Geroprotective Properties
This study (13) was conducted in 266 elderly patients (over the age of 60 years) over the course of 6 to 8 years, where some patients were treated with peptide bioregulator Thymalin, others with Epitalon and the rest were treated with the combination of the two. After the study, it was observed that both the peptides appeared to have the ability to restore basic bodily functions in geriatric patients – including improved functions in the cardiovascular, endocrinal, immune, and nervous systems, along with normalized metabolic and hemostatic activities. The peptide-treated groups appeared to exhibit a 2-fold decrease in the common geriatric disorders such as acute respiratory disorder, heart diseases and bone disorders. Additionally, the mortality rate in the peptide-treated patient appeared to significantly decrease, with a 2-fold decrease in the Thymalin treated patients, a 1.8-fold decrease in the Epitalon treated patients, and 2.5-fold decrease in the patients treated with both peptides. This study suggested that the peptide ingestion in elderly patients is likely quite safe and efficient, and could be potentially used in maintaining and treating age-related common disorders.
Epitalon Peptide Safety Profile
Studies have been conducted (on both healthy adults and geriatric patients) which have yielded results supporting the long-term efficacy and safety of the Epitalon peptide with negligible side effects. Limited side effects of the peptide have been noted during the clinical trials. Common side effects of the use of the peptide are as follows, which were observed in particularly sensitive people:
- Pain, swelling and redness at the administration site
- Temporary flu-like symptoms
A randomized clinical trial (14) was conducted for 12 years on elderly patients suffering from coronary disease and increased aging of the cardiovascular system. Some elderly patients were treated with the Epitalon peptide, for 12 continuous years, and some patients were part of the control group (i.e., not treated with the peptide, but monitored for 12 years). During these 12 years, the number of elderly patients who died (due to natural causes) were 28% less in the peptide-treated group, despite the basic therapy in both groups being identical. There appeared to be a 2-fold decrease in cardiovascular failure and respiratory diseases in the peptide treated elderly patients. No severe adverse events were reported during this study. This study suggested that the peptide not only possessed geroprotective properties but could be used long term in the life prognosis of the old patients without any severe adverse effect.
All studies conducted in geriatric patients have yielded positive outcomes – causing restoration of the bodily functions to normal rate (which otherwise decline with increasing age) and decline in the rate of common disorders caused in elderly patients. Consequently, it has been suggested that Epitalon may cause a decrease in the mortality rate with no severe adverse effects, making it a promising candidate in the medical field for treating old patients. That said, Epitalon, and all peptides mentioned in this article, are still under investigation and have not been approved for human consumption. The Epitalon available here is for research purposes only, not personal use, and this article is provided only for educational purposes.
1. Khavinson VKh. Peptides and Ageing. Neuro Endocrinol Lett. 2002;23 Suppl 3:11-144. PMID: 12374906. https://pubmed.ncbi.nlm.nih.gov/12374906/
2. Khavinson, Vladimir et al. “AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism.” Molecules (Basel, Switzerland) vol. 25,3 609. 30 Jan. 2020, doi:10.3390/molecules25030609. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037223/
3. Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003 Jun;135(6):590-2. doi: 10.1023/a:1025493705728. https://pubmed.ncbi.nlm.nih.gov/12937682/
4. Khavinson VKh, Kuznik BI, Tarnovskaia SI, Lin’kova NS. [Peptides and CCL11 and HMGB1 as molecular markers of aging: literature review and own data]. Adv Gerontol. 2014;27(3):399-406. Russian. https://pubmed.ncbi.nlm.nih.gov/25826983/
5. Lin’kova, N.S., Drobintseva, A.O., Orlova, O.A. et al. Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro . Bull Exp Biol Med 161, 175–178 (2016).
6. Khavinson VKh, Bondarev IE, Butyugov AA, Smirnova TD. Peptide promotes overcoming of the division limit in human somatic cell. Bull Exp Biol Med. 2004 May;137(5):503-6. doi: 10.1023/b:bebm.0000038164.49947.8c. PMID: 15455129. https://pubmed.ncbi.nlm.nih.gov/15455129/
7. Khavinson VKh, Lezhava TA, Monaselidze JR, Jokhadze TA, Dvalishvili NA, Bablishvili NK, Trofimova SV. Peptide Epitalon activates chromatin at the old age. Neuro Endocrinol Lett. 2003 Oct;24(5):329-33. PMID: 14647006. https://pubmed.ncbi.nlm.nih.gov/14647006/
8. Rosenfeld SV, Togo EF, Mikheev VS, Popovich IG, Khavinson VKh, Anisimov VN. Effect of Epithalon on the incidence of chromosome aberrations in senescence-accelerated mice. Bull Exp Biol Med. 2002 Mar;133(3):274-6. doi: 10.1023/a:1015899003974. PMID: 12360351. https://pubmed.ncbi.nlm.nih.gov/12360351/
9. Kossoy G, Anisimov VN, Ben-Hur H, Kossoy N, Zusman I. Effect of the synthetic pineal peptide Epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo. 2006 Mar-Apr;20(2):253-7. PMID: 16634527. https://pubmed.ncbi.nlm.nih.gov/16634527/
10. Pateyk AV, Baranchugova LM, Rusaeva NS, Obydenko VI, Kuznik BI. Effect of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the morphology of the thymus in hypophysectomized young and old birds. Bull Exp Biol Med. 2013 Mar;154(5):681-5. doi: 10.1007/s10517-013-2029-0. PMID: 23658898. https://pubmed.ncbi.nlm.nih.gov/23658898/
11. Korkushko OV, Lapin BA, Goncharova ND, Khavinson VKh, Shatilo VB, Vengerin AA, Antoniuk-Shcheglova IA, Magdich LV. [Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people]. Adv Gerontol. 2007;20(1):74-85. Russian
12. Khavinson V, Razumovsky M, Trofimova S, Grigorian R, Razumovskaya A. Pineal-regulating tetrapeptide Epitalon improves eye retina condition in retinitis pigmentosa. Neuro Endocrinol Lett. 2002 Aug;23(4):365-8. PMID: 12195242. https://pubmed.ncbi.nlm.nih.gov/12195242/
13. Khavinson VKh, Morozov VG. Geroprotektornaia éffektivnost’ timalina i épitalamina [Geroprotective effect of thymalin and Epithalamin]. Adv Gerontol. 2002;10:74-84. Russian. PMID: 12577695. https://pubmed.ncbi.nlm.nih.gov/12577695/
14. Korkushko OV, Khavinson VKh, Shatilo VB, Antonyuk-Shcheglova IA. Geroprotective effect of Epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging. Bull Exp Biol Med. 2006 Sep;142(3):356-9. English, Russian. doi: 10.1007/s10517-006-0365-z. PMID: 17426848. https://pubmed.ncbi.nlm.nih.gov/17426848/
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Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.