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 properties:
- May enhance sleep by stimulating the pineal gland, releasing more melatonin
- May stimulate the generation of telomerase
- 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 suggested to be functional in increasing melatonin production, improving the immunological and anti-carcinogenic functions in rats and mice, and restoring reproductive function in old rodents. Similar actions of this naturally occurring peptide were observed in clinical studies. Utilizing the recent advancements in science, a peptide similar to Epithalamin was synthesized and titled ‘Epitalon.’ Epitalon is derived from a naturally occurring peptide belonging to both pineal gland and eye retina. (1)
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 action similar to Epithalamin via various modes. This potential mechanism and further studies are described below.
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 tissue, which then interact with the DNA. This potential 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 ligament stem cells may potentially lead to enhanced functionality.
Epitalon Peptide and Anti-Aging
In order to understand the anti-aging action of various synthetic peptides, studies have been widely conducted to study their potential 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.
Epitalon Peptide and Fetal Studies
This study (6) was conducted to understand the proliferative potential of the peptide on 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 presented 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 appeared to cause 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 the cells (6).
Epitalon Peptide and Lymphocytic Cells
In this clinical study (7), lymphocytic cells were isolated and cultured from subjects aged between 76 and 80 years. The purpose of this study was to determine the action of Epitalon on ribosomal cell activity and its impact on denaturation and polymorphism of heterochromatin. The outcome of this study, following the delivery 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 potential to modify the chromosome regions in the aging cells, activate chromatin, and restore cellular activities that were otherwise suppressed or delayed in geriatric subjects.
Epitalon Peptide and Anti-Mutagenic Action
In this 2011 study (8), three different mice models were used to determine the action 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 delivery 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 presented 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. In combination with melatonin at night, given with water, there was no reported impact on the action of the peptide. This study suggested that Epitalon may possess anti-mutagenic potential.
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 presented five times in a week. Once the study was completed, it was reported that three out of the nine mice in the control group appeared to exhibit metastasis and an increase in the number of tumor cells. Meanwhile, the peptide mice exhibited a decrease in the number of tumor cells. Epitalon, upon delivery, appeared to inhibit the process of metastasis in the mice, preventing tumor cell cycle and growth. Researchers of this study posited the anti-metastatic potential of the peptide.
Epitalon Peptide and Research in Hypophysectomized Birds
In this study (10), hypophysectomized birds, both young and old, were selected to study the action of Epitalon peptide on the morphology of thymus gland. Hypophysectomized birds are birds in which the pituitary gland has been surgically removed. Upon delivery 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 improved results were observed on birds (mainly chickens) that underwent a neonatal hypophysectomy before the peptide was presented.
Epitalon Peptide and Melatonin Levels
This study (11) was carried out on both aging monkeys and clinical subjects 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 delivery of Epitalon, it appeared to stimulate action 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 subjects.
Epitalon Peptide and Retinal Cells
In this clinical study (12), it was suggested that when Epitalon was presented in geriatric subjects, 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 older subjects, which is supported by the positive clinical outcome in 90% of the subjects presented with the peptide.
Epitalon and Geroprotective Properties
This study (13) was conducted in 266 elderly subjects (over the age of 60 years) over the course of 6 to 8 years, where some subjects were presented with peptide-bioregulator Thymalin, others with Epitalon, and the rest with the combination of the two. After the study, it was observed that both the peptides appeared to have the potential to restore basic bodily functions in geriatric subjects – including improved functions in the cardiovascular, endocrinal, immune, and nervous systems, along with normalized metabolic and hemostatic activities. The peptide 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 subjects appeared to significantly decrease, with a 2-fold decrease in the Thymalin subjects, a 1.8-fold decrease in the Epitalon subjects, and 2.5-fold decrease in the subjects presented with both peptides.
Epitalon peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.
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.