Pineal Peptide Research

Epitalon: Ala-Glu-Asp-Gly Tetrapeptide Research Data

A conservative review of Epitalon (Epithalon, AEDG): its chemistry and Epithalamin lineage, the cell-culture telomerase data, the St. Petersburg animal studies, the 2025 independent replication, and where regulators stand in 2026.

·
Fact-checked · Reviewed by Remy Research Editorial Board
Update History ▾
October 6, 2026: Initial publication, built from a source-by-source check of the Epitalon literature, FDA's 2026 briefing documents and the July 2026 advisory-committee vote. It separates cell-culture, animal and human evidence, and flags which findings come from a single research network.
Research-use-only framing applied throughout in line with Remy editorial standards.
TL;DR — Research Summary

Epitalon (Ala-Glu-Asp-Gly) is a synthetic tetrapeptide derived from a pineal-gland extract, with a long St. Petersburg research record, a cell-culture telomerase signal, and no registered human trials. Vladimir Khavinson's group reported that it induced telomerase activity and telomere elongation in human fetal fibroblasts, and that treated cultures kept dividing after control cells had stopped.[1][2] An independent UK team reported in 2025 that Epitalon raised telomerase activity and average telomere length in two normal human cell lines and lengthened telomeres through a different pathway in breast-cancer lines; the paper's main figures were later corrected.[3][4] The rodent lifespan and tumour studies come almost entirely from one research network, and their results are mixed.[5]

FDA's 2026 review found no clinical studies assessing Epitalon's safety in humans.[6] Epitalon is not an approved medicine in the US or EU, and material supplied by Remy Research is for in-vitro laboratory research only — not for human or veterinary use.

Compliance note: this page is a research review, not a treatment guide. It does not provide human-use dosing, therapeutic recommendations, or any clinical-use instructions, and should be read in the same non-therapeutic frame required across Remy's research content.

What Is Epitalon?

Epitalon — also written Epithalon or Epithalone, and abbreviated AEDG — is a synthetic tetrapeptide with the sequence alanine, glutamic acid, aspartic acid, glycine (H-Ala-Glu-Asp-Gly-OH). PubChem lists the free base as C14H22N4O9, with a molecular weight of about 390.35 g/mol, CAS number 307297-39-8, and PubChem CID 219042.[7] FDA's 2026 briefing document lists the acetate salt separately (CAS 307297-40-1, about 450.40 g/mol) and gives the free base the FDA substance code (UNII) O65P17785G.[6]

Two identity cautions matter when reading the literature. PubChem's synonym list for the same entry also carries "Epithalamin", the name of the pineal extract Epitalon was designed from, but FDA's substance registry does not treat the two as the same substance.[6] And there is no international nonproprietary name: FDA notes the peptide circulates under inconsistent naming, and that published papers often do not say whether they used the free base or the acetate salt.[6]

From Epithalamin to Epitalon

Epitalon descends from Epithalamin, a crude polypeptide extract of bovine pineal glands that Khavinson's St. Petersburg group studied for decades in experimental gerontology and oncology.[8] The tetrapeptide was designed from the amino-acid composition of that extract, as a defined, synthesizable molecule.[9] FDA's account adds a practical driver: the limited supply of calf pineal glands needed to make the extract.[6]

Khavinson's international patent application for the tetrapeptide was filed on 20 January 2000 and later issued in the US as patent 6,727,227.[10] In 2017 the same group reported detecting AEDG by mass spectrometry in a pineal polypeptide complex, which is the basis for later descriptions of Epitalon as "naturally occurring".[11] That is a single-group analytical report, not a demonstration of the peptide in human pineal tissue.

The distinction matters because the longest human data — the mortality follow-ups discussed below — used the Epithalamin extract, not Epitalon. Those results cannot be attributed to the synthetic tetrapeptide.

Proposed Mechanisms and the Evidence Behind Each

Epitalon has been linked to several pathways rather than a single receptor. The table sorts each proposed mechanism by the kind of evidence behind it and by who produced it.

Epitalon — Proposed Mechanisms and Evidence
Proposed mechanism What was reported Evidence and source
Telomerase (hTERT) Higher hTERT expression and telomerase activity in human fetal fibroblasts and in two normal human cell lines; telomerase activation reported in bovine embryos Cell culture only; Khavinson group plus independent UK and Korean labs
Telomere length Longer telomeres in fetal fibroblasts; longer average telomeres by qPCR in normal cell lines; lengthening through the ALT pathway in breast-cancer lines Cell culture only; Khavinson group plus an independent UK lab
Replicative lifespan Treated fibroblasts reached passage 44, against passage 34 in controls Cell culture; Khavinson group only
Melatonin Higher melatonin in rat pinealocyte culture and senescent monkeys; no effect on melatonin secretion from perifused rat pineal glands in a Paris study Cell culture, ex vivo, animal and small human reports; results conflict
Oxidative stress Lower reactive oxygen species and preserved mitochondrial function in aging mouse oocytes Cell culture; independent Chinese lab
Tumour biology Fewer spontaneous tumours and smaller mammary tumours in mice Animal; Khavinson–Anisimov network

No receptor has been identified. The 2025 independent review by Araj and colleagues in Warsaw describes the mechanism as unclear and notes that physico-chemical and structural work on the peptide is very limited.[9]

The Telomere Evidence, Study by Study

1. Telomerase Induction in Fetal Fibroblasts (Khavinson et al. 2003)

In telomerase-negative human fetal lung fibroblasts, the group reported that Epitalon induced expression of the telomerase catalytic subunit, telomerase activity and telomere elongation.[1]

2. Past the Division Limit (Khavinson et al. 2004)

A follow-up study reported that control fibroblasts stopped dividing at passage 34, while treated cultures reached passage 44 — about ten extra divisions — with telomere length back to early-passage values.[2] No independent group has published a replication of this result.

3. The Independent Replication (Al-Dulaimi et al. 2025)

A Brunel University London team with no Khavinson co-authors tested Epitalon from a commercial supplier in two normal human cell lines (IBR.3 fibroblasts and HMEC epithelial cells) and two breast-cancer lines.[3] In the normal cells it reported higher hTERT mRNA, higher telomerase activity and longer average telomeres. In the cancer lines, telomeres lengthened through the ALT (Alternative Lengthening of Telomeres) pathway, while telomerase activity did not rise significantly.

Three caveats limit how far the paper can be read. The normal cells were tested at a single concentration, so it does not show a dose response in normal cells. Telomere length was measured by qPCR, which averages across all chromosomes — a limitation the authors acknowledge. And a November 2025 correction replaced the paper's Figures 1–3.[3][4]

4. Independent Reproductive-Cell Studies

Two other independent groups used Epitalon in reproductive-cell models. A 2022 Chinese study reported lower reactive oxygen species, fewer spindle defects and preserved mitochondrial function in aging mouse oocytes in vitro.[12] A 2025 Korean study reported a higher bovine oocyte maturation rate, better post-thaw embryo development and telomerase activation.[13]

Taken together, more than one laboratory has now reported a telomerase signal, but only in cell culture. No study measuring telomere length in animals or humans after Epitalon exposure was found.

Animal Studies: Lifespan, Tumours and Melatonin

Most in-vivo work comes from Anisimov and Khavinson's collaboration, and the lifespan results do not point one way:

Melatonin is the other recurring endpoint. The group reported higher evening melatonin and a normalised cortisol rhythm in senescent rhesus monkeys, and higher melatonin output in rat pinealocyte culture.[17][18] A Paris study with the same co-authors found no significant effect on melatonin secretion from perifused pineal glands of young or old rats.[19] FDA's 2026 review concluded that how Epitalon might affect melatonin in a living body remains unknown.[6]

Human Data: What Exists and What Does Not

The best-known human results concern the Epithalamin extract. In 79 elderly patients with accelerated cardiovascular ageing, Khavinson's group and the Institute of Gerontology in Kyiv reported lower all-cause and cardiovascular mortality in the extract group at 12- and 15-year follow-ups.[20][21] Those findings belong to the extract, not to Epitalon.

For Epitalon itself, the human record is a handful of small Khavinson-group reports, mostly measuring melatonin. The largest, a 2020 Russian-language study of 75 middle-aged adults, reported a 1.7-fold rise in a urinary melatonin metabolite; FDA notes that it did not report safety data.[22][6]

There are no registered trials: ClinicalTrials.gov returns no studies for Epitalon or its synonyms.[23] FDA's 2026 briefing found no clinical studies assessing Epitalon's safety in humans, no pharmacokinetic data and no reports in its adverse-event database.[6]

Who Did the Research

Author concentration is the most important context for this literature. Of 144 PubMed records that mention Epitalon or its synonyms in the title or abstract, 94 (65%) list Khavinson or V.N. Anisimov as an author, and many of the rest come from the same institute.[24] The Alzheimer's Drug Discovery Foundation adds that at least half of the roughly 110 papers on Epithalamin and Epitalon are in Russian.[8]

Independent primary studies are few, and all three are cell-culture work: the 2022 oocyte study, the 2025 bovine-embryo study and the 2025 UK telomere study.[12][13][3] The 2025 review by Araj and colleagues is the main independent review.[9] There is still no independent animal-lifespan study and no independent human study.

Regulatory Status in 2026

Where Epitalon stands as of October 6, 2026.
  • United States. Epitalon is not FDA-approved and is not on the 503A Bulks List. FDA placed it in Category 2 ("may present significant safety risks") in September 2023 and removed it in April 2026 only because its nominations were withdrawn; that did not make it compoundable.[25][26] On July 24, 2026 FDA's Pharmacy Compounding Advisory Committee voted 7–4, with one abstention, to recommend adding Epitalon to the Bulks List for insomnia, against the recommendation of FDA's reviewers.[27][28] Advisory votes are non-binding, and listing requires notice-and-comment rulemaking; no proposed rule had appeared by October 6, 2026.
  • European Union and Russia. No EU authorisation was found. FDA's 2026 review records no recognition of Epitalon in other countries or foreign pharmacopoeias; older sources describe the extract Epithalamin, not Epitalon, as approved in Russia.[26][8]
  • United Arab Emirates. No UAE registration was found.
  • Sport. Epitalon is not named on WADA's Prohibited List, but class S0 bans at all times any substance without government approval for human therapeutic use, and the 2027 list names "peptides" among its examples.[29]

What the Epitalon Literature Does Not Yet Give You

These gaps are not arguments against studying Epitalon. They are arguments against overselling it.

Where Epitalon Fits in an RUO Research Catalog

For research use, Epitalon belongs with the pineal and ageing-biology peptide research tools: a defined tetrapeptide for cell-culture and model work on telomerase, melatonin and oxidative-stress endpoints. Remy Research lists it as the Genovare Epitalon 100mg AQ pen, supplied for in-vitro laboratory research only. It is not framed for human use, veterinary use or treatment.

For researchers reading this page as a starting point, the most useful adjacent references on this site are the peptide primer, the FOXO4-DRI senolytic review, the MOTS-c mitochondrial review, the COA and HPLC purity guide, and the Dubai legality brief.

Our Research Standards

This article prioritizes primary literature, FDA's 2026 briefing documents and independent reviews, and flags which findings come from a single research network. Where the human record is thin or absent, we say so directly. No therapeutic, human-use, or veterinary-use claim is made here. Read our editorial policy →

RP
Editorial Review

Editorial Board, Remy Research

The Remy Research Editorial Board reviews Remy's peptide research library, with a focus on analytical verification, clinical-trial interpretation, and compliance-safe scientific communication.

About the editorial team →

Epitalon Research FAQ

What is Epitalon?

Epitalon (also Epithalon, Epithalone or AEDG) is a synthetic tetrapeptide with the sequence Ala-Glu-Asp-Gly. PubChem lists the free base as C14H22N4O9, about 390.35 g/mol, CAS 307297-39-8. Vladimir Khavinson's St. Petersburg group designed it from the amino-acid composition of Epithalamin, a bovine pineal-gland extract. It is a research compound, not an approved medicine.[7][9]

Is Epitalon the same as Epithalamin?

No. Epithalamin is a crude polypeptide extract of bovine pineal glands; Epitalon is one defined synthetic tetrapeptide, and FDA's substance registry does not treat them as synonyms. The long-term human mortality data from St. Petersburg and Kyiv used Epithalamin, so those results cannot be attributed to Epitalon.[6][21]

Does Epitalon lengthen telomeres?

So far only in cell culture. Khavinson's group reported telomerase induction and telomere elongation in human fetal fibroblasts, and an independent UK study in 2025 reported higher telomerase activity and average telomere length in two normal human cell lines; that paper's main figures were later corrected. No animal or human study measuring telomere length after Epitalon was found.[1][3][4]

Has Epitalon been tested in humans?

Only in a few small Khavinson-group studies, mostly measuring melatonin or its urinary metabolite. FDA's 2026 review found no clinical studies assessing Epitalon's safety in humans and no pharmacokinetic data, and ClinicalTrials.gov lists no registered Epitalon trials.[6][23]

Did the FDA approve Epitalon in 2026?

No. On July 24, 2026 FDA's Pharmacy Compounding Advisory Committee voted 7–4, with one abstention, to recommend adding Epitalon to the 503A Bulks List for insomnia, against the recommendation of FDA's reviewers. The vote is non-binding and concerns pharmacy compounding, not drug approval, and no proposed rule had appeared by October 6, 2026.[27][28]

Is Epitalon an approved medicine anywhere?

No approval was found. FDA's 2026 review records no recognition of Epitalon in other countries or foreign pharmacopoeias, and no EU authorisation was found.[26]

Is Epitalon banned in sport?

It is not named on WADA's Prohibited List, but class S0 bans at all times any pharmacological substance without current government approval for human therapeutic use, and from January 1, 2027 the S0 examples explicitly include peptides. No approval for Epitalon was found.[29]

Is Epitalon safe?

That has not been established. FDA concluded it lacks sufficient information to know whether Epitalon would cause harm in humans, and flagged immunogenicity concerns, incomplete chemical characterization and a theoretical cancer concern because the peptide activates telomerase. Khavinson-group mouse studies reported no toxicity and fewer tumours, but they have not been independently replicated.[25][6][5]

Sources

  1. Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003;135(6):590-592. doi: 10.1023/a:1025493705728 · PMID: 12937682 ↩
  2. Khavinson VKh, Bondarev IE, Butyugov AA, Smirnova TD. Peptide promotes overcoming of the division limit in human somatic cell. Bull Exp Biol Med. 2004;137(5):503-506. doi: 10.1023/b:bebm.0000038164.49947.8c · PMID: 15455129 ↩
  3. Al-Dulaimi S, Thomas R, Matta S, Roberts T. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology. 2025;26(5):178. doi: 10.1007/s10522-025-10315-x · PMID: 40908429 ↩
  4. Al-Dulaimi S, Thomas R, Matta S, Roberts T. Correction: Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology. 2025;27(1):1. doi: 10.1007/s10522-025-10326-8 · PMID: 41240216 ↩
  5. Anisimov VN, Khavinson VKh, Popovich IG, et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology. 2003;4(4):193-202. doi: 10.1023/a:1025114230714 · PMID: 14501183 ↩
  6. U.S. Food and Drug Administration. Briefing document on epitalon (free base) and epitalon acetate for the July 2026 Pharmacy Compounding Advisory Committee meeting, dated May 12, 2026. fda.gov/media/193345 ↩
  7. National Center for Biotechnology Information. PubChem Compound Summary for CID 219042, Epitalon. pubchem.ncbi.nlm.nih.gov/compound/219042 ↩
  8. Alzheimer's Drug Discovery Foundation. Cognitive Vitality for Researchers: Epithalamin and Epithalon. Last updated October 10, 2023. alzdiscovery.org ↩
  9. Araj SK, Brzezik J, Mądra-Gackowska K, Szeleszczuk Ł. Overview of Epitalon — Highly Bioactive Pineal Tetrapeptide with Promising Properties. Int J Mol Sci. 2025;26(6):2691. doi: 10.3390/ijms26062691 · PMID: 40141333 ↩
  10. Khavinson VK. Tetrapeptide revealing geroprotective effect, pharmacological substance on its basis, and the method of its application. US Patent 6,727,227 B1; international application PCT/RU00/00012 filed January 20, 2000. uspto.gov ↩
  11. Khavinson VK, Kopylov AT, Vaskovsky BV, et al. Identification of Peptide AEDG in the Polypeptide Complex of the Pineal Gland. Bull Exp Biol Med. 2017;164(1):41-43. doi: 10.1007/s10517-017-3922-8 · PMID: 29124531 ↩
  12. Yue X, Liu SL, Guo JN, et al. Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro. Aging (Albany NY). 2022;14(7):3191-3202. doi: 10.18632/aging.204007 · PMID: 35413689 ↩
  13. Ullah S, Haider Z, Perera CD, et al. Epitalon-activated telomerase enhance bovine oocyte maturation rate and post-thawed embryo development. Life Sci. 2025;362:123381. doi: 10.1016/j.lfs.2025.123381 · PMID: 39788414 ↩
  14. Anisimov VN, Khavinson VK, Mikhalski AI, Yashin AI. Effect of synthetic thymic and pineal peptides on biomarkers of ageing, survival and spontaneous tumour incidence in female CBA mice. Mech Ageing Dev. 2001;122(1):41-68. doi: 10.1016/s0047-6374(00)00184-6 · PMID: 11163623 ↩
  15. Vinogradova IA, Bukalev AV, Zabezhinski MA, et al. Geroprotective effect of ala-glu-asp-gly peptide in male rats exposed to different illumination regimens. Bull Exp Biol Med. 2008;145(4):472-477. doi: 10.1007/s10517-008-0121-7 · PMID: 19110597 ↩
  16. Anisimov VN, Khavinson VK, Provinciali M, et al. Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer. 2002;101(1):7-10. doi: 10.1002/ijc.10570 · PMID: 12209581 ↩
  17. Khavinson V, Goncharova N, Lapin B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro Endocrinol Lett. 2001;22(4):251-254. PMID: 11524632 ↩
  18. Khavinson VKh, Linkova NS, Kvetnoy IM, et al. Molecular cellular mechanisms of peptide regulation of melatonin synthesis in pinealocyte culture. Bull Exp Biol Med. 2012;153(2):255-258. doi: 10.1007/s10517-012-1689-5 · PMID: 22816096 ↩
  19. Djeridane Y, Khavinson VKh, Anisimov VN, Touitou Y. Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats. J Endocrinol Invest. 2003;26(3):211-215. doi: 10.1007/BF03345159 · PMID: 12809170 ↩
  20. Korkushko OV, Khavinson VKh, Shatilo VB, et al. Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging. Bull Exp Biol Med. 2006;142(3):356-359. doi: 10.1007/s10517-006-0365-z · PMID: 17426848 ↩
  21. Korkushko OV, Khavinson VKh, Shatilo VB, et al. Peptide geroprotector from the pituitary gland inhibits rapid aging of elderly people: results of 15-year follow-up. Bull Exp Biol Med. 2011;151(3):366-369. doi: 10.1007/s10517-011-1332-x · PMID: 22451889 ↩
  22. Ivko OM, Linkova NS, Ilina AR, et al. AEDG peptide regulates human circadian rhythms genes expression during pineal gland accelerated aging [in Russian]. Adv Gerontol. 2020;33(3):429-435. PMID: 33280326 ↩
  23. ClinicalTrials.gov search for epitalon, epithalon, epithalone, epithalamin or "Ala-Glu-Asp-Gly", run October 6, 2026 (0 studies). clinicaltrials.gov ↩
  24. PubMed title/abstract search for epitalon, epithalon, epithalone or "Ala-Glu-Asp-Gly", run October 6, 2026 (144 records; 94 with Khavinson or V.N. Anisimov as an author). pubmed.ncbi.nlm.nih.gov ↩
  25. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (Epitalon listed under "nominated but withdrawn"; page modified April 22, 2026). fda.gov ↩
  26. Health Affairs Forefront. Analysis of FDA briefing documents and the July 2026 Pharmacy Compounding Advisory Committee peptide votes, August 4, 2026. doi: 10.1377/forefront.20260803.287322. healthaffairs.org ↩
  27. U.S. Food and Drug Administration. July 23–24, 2026: Meeting of the Pharmacy Compounding Advisory Committee (Docket FDA-2025-N-6895). fda.gov ↩
  28. McDermott Will & Schulte. Summary of the July 23–24, 2026 PCAC peptide votes, July 27, 2026. mcdermottlaw.com ↩
  29. World Anti-Doping Agency. 2027 Prohibited List, class S0 Non-Approved Substances (in force January 1, 2027). wada-ama.org ↩
  30. Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266(5193):2011-2015. doi: 10.1126/science.7605428 · PMID: 7605428 ↩

For catalog details, see the Genovare Epitalon 100mg AQ pen. For compliance context, continue to the Dubai legality brief and the research standards page.

Related Research

Senolytic FOXO4-DRI Senolytic Peptide Research→ Sleep Peptide DSIP Delta Sleep-Inducing Peptide Research→ Mitochondrial MOTS-c Mitochondrial Peptide Research→ Catalog Genovare Epitalon 100mg AQ Pen→ Nootropic Semax Peptide Research→ Primer What Are Peptides?→ Verification Peptide COA & HPLC Purity Guide→ Compliance Are Peptides Legal in Dubai?→ Catalog Research Peptide Catalog→