Everything below concerns epithalamin. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2026-08-01. Where a claim depends on a specific study, the study is described rather than over-claimed.
Material supplied for laboratory use is normally a lyophilised white to off-white powder that dissolves readily in water and in isotonic saline. Lyophilised cakes are hygroscopic and should be equilibrated to room temperature before opening to limit condensation on the solid. Solutions are typically prepared at milligram-per-millilitre concentrations and divided into single-use aliquots, because repeated freeze–thaw cycles degrade short peptides. Aqueous solutions are far less stable than the dry powder, and identity is usually verified by mass spectrometry alongside purity estimation from reversed-phase high-performance liquid chromatography.
Epitalon is a synthetic linear tetrapeptide with the sequence alanine–glutamate–aspartate–glycine, abbreviated AEDG. Its molecular formula is C14H22N4O9 and the calculated mass is approximately 390.35 g/mol. The compound is made by solid-phase peptide synthesis rather than extracted from tissue, although early work described it as a short fragment of a peptide fraction obtained from bovine pineal extract. In the research literature the spelling epitalon and the variant epithalone both appear, while AEDG is the standard code used in peptide nomenclature.
Several names circulate for the same molecule, including epitalon, epithalone, epithalamin tetrapeptide, and the sequence code AEDG. A CAS registry number, 307297-39-8, is commonly cited for it, though catalogue entries should be checked against supplier documentation because mislabelled records occur. In its usual form the peptide carries free amino and carboxyl termini and is neither glycosylated nor lipidated. Researchers distinguish the defined tetrapeptide from epithalamin itself, a crude pineal preparation containing many peptides that is not chemically characterised.
Verification of research-grade material involves comparing a supplier chromatogram against an in-house reference, checking the observed mass against the calculated value, and where possible confirming residue order by tandem mass spectrometry or enzymatic peptide mapping. Purity claims should be read alongside the method used to obtain them, because detection wavelength and integration settings alter the result. Batch-specific data, rather than a generic grade statement, is the informative part of a certificate.
Identity and purity of epitalon samples are normally established by reversed-phase high-performance liquid chromatography with ultraviolet detection near 214 nanometres, combined with mass spectrometry. The mass spectrum confirms the expected molecular ion and can reveal truncated or oxidised by-products. Amino acid analysis after acid hydrolysis verifies that the four residues are present in the expected ratio. Certificates typically report a purity figure taken from chromatographic peak area, expressed as a percentage of total integrated signal.
Lyophilised epitalon is generally held at minus twenty degrees Celsius in a sealed container kept dry and dark. Cooler conditions are sometimes recommended for long-term archives. The solid takes up moisture readily enough that repeated opening of a vial introduces water, so dividing a batch into smaller portions before storage lowers degradation risk. Aqueous solutions are less durable than the dry powder and are usually prepared shortly before use, then kept cold and shielded from light to slow hydrolysis and oxidation.
| Property | Value | Notes |
|---|---|---|
| Amino acid sequence | Ala-Glu-Asp-Gly | Linear tetrapeptide, also written AEDG |
| Molecular mass | About 390.35 g/mol | Value calculated from the sequence |
| Appearance | White to off-white powder | Lyophilised material forms a loose cake |
| Solubility | Freely soluble in water | Also dissolves in isotonic saline |
| Storage | -20 °C, desiccated | Aliquot solutions to avoid freeze–thaw cycling |
Discussions in the literature often conflate three distinct entities: the pineal extract epithalamin, the isolated tetrapeptide AEDG, and commercial preparations sold under similar names. Reviews citing older Russian-language studies sometimes omit detail on purity, route of administration and control groups, which makes cross-study comparison difficult. Researchers working with the compound generally note the need for independent replication, standardized enzyme assays, and clearer reporting of peptide identity. These caveats are relevant when weighing claims that appear in secondary sources rather than in primary reports.
（TG:@pojiaai）Epitalon is a synthetic linear tetrapeptide with the sequence alanine-glutamate-aspartate-glycine, abbreviated AEDG. It emerged from work on epithalamin, a peptide fraction prepared from bovine pineal tissue, and was designed as a short, chemically defined analogue of that extract. Early publications came mainly from Russian laboratories studying pineal peptides and aging-related endpoints. The compound appears in the literature under several spellings, including epithalon and epithalone, which complicates systematic searching. Its small size makes solid-phase assembly and routine analytical characterization straightforward.
Chemically, the molecule consists of four amino acid residues joined by three peptide bonds, with a free N-terminal amino group and a free C-terminal carboxyl group. Its molecular formula is C14H22N4O9, and its monoisotopic mass is approximately 390 daltons. The acidic glutamate and aspartate side chains give the peptide a net negative charge near neutral pH, a property that shapes its chromatographic behaviour and solubility profile. No disulfide bridges or other post-translational modifications are present, so the primary sequence alone defines the structure.
Freeze-dried epitalon is normally kept at minus twenty degrees Celsius in a sealed, desiccated container, protected from light. Short excursions at ambient temperature during shipping are generally tolerated, but repeated warming and cooling cycles encourage moisture uptake, which shortens shelf life. Once dissolved, the peptide is far less stable than the solid: aqueous solutions are subject to hydrolysis and to deamidation at the aspartate and glutamate residues. Working solutions are therefore held refrigerated and used within days, and repeated freezing and thawing of the same vial is best avoided.
Identity and purity are checked by reversed-phase high-performance liquid chromatography, usually with ultraviolet detection near 214 nanometres, where the peptide bond absorbs. Mass spectrometry confirms the expected mass and reveals whether truncation products or adducts are present. Acid hydrolysis followed by amino acid analysis gives the residue ratio, which should approximate one alanine, one glutamate, one aspartate and one glycine. Counter-ions such as acetate or trifluoroacetate remain in the dried product and lower net peptide content, so a stated purity figure on a label does not by itself describe how much peptide a vial holds.
Proposed mechanisms centre on cell-culture observations rather than a defined receptor interaction. Several reports describe increased expression of the telomerase catalytic subunit after exposure of cultured human cells, and the authors attributed the effect to short peptide fragments entering the nucleus and influencing gene transcription. No receptor for the tetrapeptide has been identified, and the free peptide is expected to be degraded rapidly by plasma peptidases. Whether any measurable fraction reaches intact tissues after administration remains an unresolved question rather than an established finding.
The published literature is dominated by a small number of research groups, much of it in Russian-language journals, and independent replication outside those groups is limited. Studies are typically small, use cultured cells or rodent models, and report endpoints that differ between papers, which makes comparison difficult. Large randomised human trials have not appeared in the indexed literature. Questions about absorption, distribution and clearance are therefore still treated as open in reviews that mention the compound.
Epitalon is a synthetic tetrapeptide with the sequence alanine–glutamate–aspartate–glycine, commonly abbreviated AEDG. Its design traces to epithalamin, a peptide fraction prepared from bovine pineal gland extracts that researchers in Saint Petersburg began investigating in the 1970s. The compound has a molecular formula of C14H22N4O9 and a nominal molecular mass near 390 daltons. It holds no approved drug status in the United States or the European Union, and material sold under this name is generally offered as a research chemical rather than a finished pharmaceutical product.
Reference material is normally supplied as a lyophilised powder in a sealed vial. Product literature typically recommends storage at minus twenty degrees Celsius or colder, protected from light and moisture. Freeze-thaw cycling is usually avoided because repeated condensation can introduce water into the vial. Working solutions are commonly prepared fresh, aliquoted, and kept cold for short periods rather than stored at ambient temperature. Labelling the date of opening helps track how long a vial has been in use.
Solubility is high in water, phosphate-buffered saline and normal saline, a pattern that follows from the two acidic residues in the chain. The peptide dissolves poorly in non-polar solvents such as hexane or chloroform. Stock solutions are often prepared in water first and then diluted into the buffer of interest. Because the molecule is small and hydrophilic, filtration through a low-protein-binding membrane is usually straightforward, and visible particulates are uncommon in freshly made solutions.
Identity and purity are established with reversed-phase high-performance liquid chromatography and mass spectrometry. The chromatogram shows the main peak and any truncated or oxidised by-products, while the mass spectrum confirms the expected 390 dalton mass. Amino acid analysis can corroborate composition when a sample's origin is uncertain. Counterion content, particularly residual trifluoroacetate from purification, is frequently reported alongside purity because it shifts the net mass of the solid.
62. Neuro Endocrinol Lett. 2001 Aug;22(4):251-4. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Khavinson V(1), Goncharova N, Lapin B. Author information: (1)St. Petersburg Institute of Bioregulation and Gerontology, 3 Dynamo Prospect, 197110 St. Petersburg, Russia. ibg@medport.ru The OBJECTIVE of this research was to investigate the regulatory effect of Epitalon on the production of melatonin and cortisol in senescent monkeys. MATERIAL AND METHODS: We investigated the character of melatonin and cortisol secretion by immunoferment assay in Epitalon-administered female Macaca mulatta in different age periods. RESULTS: Epitalon was proven to significantly stimulate melatonin synthesis in senescent monkeys in the evening, thereby normalising the circadian rhythm of cortisol secretion.
36. Georgian Med News. 2006 Apr;(133):111-5. Anti-aging peptide bioregulators induce reactivation of chromatin. Lezhava T(1), Monaselidze J, Kadotani T, Dvalishvili N, Buadze T. Author information: (1)Tbilisi State University. The effect of synthetic peptide bioregulators (Epitalon, Livagen and Vilon) on structural and facultative heterochromatin of cultivated lymphocytes have been studied among old (75-88yr.) people. The data obtained indicate that epitalon, livagen and vilon: 1) activate synthetic processes, caused by reactivation of ribosomal genes as a result of deheterochromatinization (decondensation) of nucleolus organizer regions; 2) induce unrolling (deheterochromatinization) of total heterochromatin; 3) release genes repressed by heterochromatinization (condensation) of euchromatic regions forming facultative heterochromatin; 4) epitalon and livagen induce deheterochromatinization (decondensation) of pericentromeric structural heterochromatin of the chromosomes1 and 9. However, vilon does not induce deheterochromatinization of pericentromeric structural heterochromatin. These results indicate that peptide bioregulators Epitalon, Livagen and Vilon cause activation (deheterochromatinization) of chromatin in lymphocytes of old individuals.
22. Adv Gerontol. 2010;23(4):543-6. [Influence of peptides from pineal gland on thymus function at aging]. [Article in Russian] Lin'kova NS, Poliakova VO, Trofimov AV, Sevost'ianova NN, Kvetnoĭ IM. The interference between thymus and pineal gland during their involution is considered in this review. The research data about influence of thymus peptides on pineal gland and pineal peptides on thymus is summarized. Analysis of these data showed that pineal peptides (epithalamin, epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (thymalin, thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.
56. Neuro Endocrinol Lett. 2002 Aug;23(4):365-8. Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa. Khavinson V(1), Razumovsky M, Trofimova S, Grigorian R, Razumovskaya A. Author information: (1)St. Petersburg Institute of Bioregulation and Gerontology, North-Western Branch of the Russian Academy of Medical Sciences, 3 Dynamo Project, 197110 St. Petersburg, Russia. ibg@medport.ru We have studied the effect of tetrapeptide Epitalon (Ala-Glu-Asp-Gly) on the course of congenital pigmented degeneration of the retina. The application of Epitalon in Campbell rats is found to intensify the bioelectric and functional activity of the retina due to the preservation of its morphological structure. Epitalon therapy in patients with degenerative retinal lesions results in a positive clinical effect in 90% of the cases. The analysis of Epitalon effects suggests that the tetrapeptide participates in the mechanisms of transcription common for the epiphysis and retina.
62. Neuro Endocrinol Lett. 2001 Aug;22(4):251-4. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Khavinson V(1), Goncharova N, Lapin B. Author information: (1)St. Petersburg Institute of Bioregulation and Gerontology, 3 Dynamo Prospect, 197110 St. Petersburg, Russia. ibg@medport.ru The OBJECTIVE of this research was to investigate the regulatory effect of Epitalon on the production of melatonin and cortisol in senescent monkeys. MATERIAL AND METHODS: We investigated the character of melatonin and cortisol secretion by immunoferment assay in Epitalon-administered female Macaca mulatta in different age periods. RESULTS: Epitalon was proven to significantly stimulate melatonin synthesis in senescent monkeys in the evening, thereby normalising the circadian rhythm of cortisol secretion.
Sources: pubmed.ncbi.nlm.nih.gov
34. Adv Gerontol. 2006;19:72-8. [Effect of age, different light conditions, melatonin, and epitalon on lysosomal proteinase activity in the liver and kidneys of rats]. [Article in Russian] Rendakov NL, Tiutiunnik NN, Vinogradova IA. Ageing, melatonin, epithalon (tetrapeptide Ala-Glu-Asp-Gly) and different light conditions effects on protein content and cathepsins B and D activities in rat liver and kidneys lysosomal fractions were studied. Ageing leads to decrease of cathepsins activity in rat liver lysosomal fractions. Constant light and darkness conditions result in earlier age decline of cathepsins activity. Absence of day and night succession in comparison with alternating light conditions causes decline of both general and specific cathepsin D activity. Melatonin and epithalon administration resulted in decrease of cathepsin D activity in liver only under control interchangeable light conditions. Cathepsin B activity in liver and kidneys lysosomal fractions declined in all experimental light conditions. Cathepsins activity decrease under the influence of epiphysial factors is evidently connected with their inhibitory effect on protein and general metabolism.
44. Adv Gerontol. 2004;13:90-3. [Effect of epitalon on the immunity and hemostasis in hypophysectomized chicken and old hens]. [Article in Russian] Kuznik BI, Pateiuk AV, Khavinson VKh, Malinin VV. 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.
21. Adv Gerontol. 2011;24(1):38-42. [Characteristics of the pineal gland and thymus relationship in aging]. [Article in Russian] Lin'kova NS, Poliakova VO, Kvetnoĭ IM, Trofimov AV, Sevost'ianova NN. The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.
22. Adv Gerontol. 2010;23(4):543-6. [Influence of peptides from pineal gland on thymus function at aging]. [Article in Russian] Lin'kova NS, Poliakova VO, Trofimov AV, Sevost'ianova NN, Kvetnoĭ IM. The interference between thymus and pineal gland during their involution is considered in this review. The research data about influence of thymus peptides on pineal gland and pineal peptides on thymus is summarized. Analysis of these data showed that pineal peptides (epithalamin, epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (thymalin, thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.
Sources: pubmed.ncbi.nlm.nih.gov
It is a synthetic tetrapeptide. Its sequence was derived from research on peptide fractions of bovine pineal extract, and the intact AEDG sequence has not been demonstrated as an abundant free peptide in human tissue.
AEDG is the one-letter code for the four amino acids alanine, glutamate, aspartate and glycine in that order. The same molecule is written in three-letter form as Ala-Glu-Asp-Gly.
Identity is normally confirmed by mass spectrometry against the calculated mass of roughly 390.35 g/mol. Purity is then estimated by reversed-phase high-performance liquid chromatography with ultraviolet detection.
The usual approach is reversed-phase HPLC with ultraviolet detection, reported as a percentage of total peak area. Mass spectrometry is used alongside chromatography to confirm identity rather than purity alone.