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Four residues carrying the most-cited longevity claims in the peptide market — and none of them from a controlled human trial.
Also known as: Epitalon · AEDG · epithalamin related
Part of the Foundational & therapeutic peptides cluster
Overview
Epithalon (epitalon) is the synthetic tetrapeptide Ala-Glu-Asp-Gly (AEDG), designed from the amino-acid composition of epithalamin, a bovine pineal extract. Twenty-five years of mostly Russian cell and animal studies report lifespan extension in mice, telomerase induction in cultured fibroblasts and effects on melatonin and gene expression; there is no controlled human trial and it is not an approved medicine.
Source & context
Biological / chemical source: Synthetic tetrapeptide (Ala-Glu-Asp-Gly)
Primary research or clinical context: Research compound; not approved as a medicine in the US, Canada or the EU; no registered clinical trials
What epithalon is
Epithalon (also spelled epitalon or epithalone) is a four-residue synthetic peptide, Ala-Glu-Asp-Gly. It was synthesised to reproduce the amino-acid composition of epithalamin, a polypeptide extract of bovine pineal gland used in Soviet-era gerontology, before any single active peptide had been isolated from that extract (Araj et al., International Journal of Molecular Sciences 2025). It is the flagship of the Khavinson short-peptide bioregulator family and the one with the largest literature — some 56 PubMed-indexed papers, the great majority from the St Petersburg Institute of Bioregulation and Gerontology and collaborators. No IUPHAR record and no registered clinical trial exist.
Proposed mechanisms
The 2025 review summarises the mechanisms claimed over 25 years of in-vitro, in-vivo and in-silico work: antioxidant, neuroprotective and antimutagenic actions, a direct influence on melatonin synthesis, altered interleukin-2 mRNA, modulation of thymocyte mitogenic activity, and enhanced activity of enzymes including acetylcholinesterase, butyrylcholinesterase and telomerase — while stating that it remains uncertain whether these are the sole mechanisms (Araj et al., 2025). Fluorescein-labelled AEDG entered the nucleus of HeLa cells and bound DNA and oligonucleotides in vitro (Fedoreyeva et al., Biochemistry (Moscow) 2011), the basis of the group's hypothesis that short peptides regulate gene expression directly.
The telomerase claim
The most-repeated epithalon result is that adding the peptide to telomerase-negative human fetal fibroblast cultures induced expression of the telomerase catalytic subunit, telomerase enzymatic activity and telomere elongation (Khavinson et al., Bulletin of Experimental Biology and Medicine 2003). This is a single cell-culture report from the originating group. It has not been shown that epithalon reaches human cells at active concentrations after any route of administration, and no human study has measured telomere length or telomerase activity after epithalon. The marketing leap from this paper to “lengthens your telomeres” is not supported.
Animal evidence
In female HER-2/neu transgenic mice given epithalon subcutaneously five times a week from the second month of life, average and maximum lifespan increased by 13.5% and 13.9%, lifespan without neoplasms by 34.2%, lung metastases fell 1.6-fold and multiple tumours 2-fold, and the number of mice without breast tumours rose 3.7-fold (Anisimov et al., Bulletin of Experimental Biology and Medicine 2002). In old rhesus monkeys the peptide was associated with a threefold increase in nocturnal melatonin peaks (Khavinson and Golubev, Advances in Gerontology 2002). Microarray analysis of mouse heart found epithalon changed expression of 98 of 15,247 clones more than twofold (Anisimov et al., 2002). Further rat studies reported retinoprotection and altered gastrointestinal enzyme activity.
| Model | Reported effect | Source |
|---|---|---|
| HER-2/neu transgenic mice | Average lifespan +13.5%, maximum +13.9%; tumour-free lifespan +34.2%; fewer breast tumours and metastases | Anisimov et al., 2002 |
| Old rhesus monkeys | Threefold increase in nocturnal melatonin peaks | Khavinson & Golubev, 2002 |
| Mouse heart microarray | 98 of 15,247 clones changed >2-fold | Anisimov et al., 2002 |
| Human fetal fibroblasts (culture) | Telomerase activity and telomere elongation induced | Khavinson et al., 2003 |
Human evidence
No randomised, placebo-controlled trial of epithalon has been published, and none is registered on ClinicalTrials.gov. The 2025 review, which is favourable in tone, still notes that the mechanisms are uncertain and that the evidence base is in-vitro, in-vivo and in-silico. Historical Russian reports on the parent extract epithalamin in elderly patients are outside the scope of this profile and do not establish anything about the synthetic tetrapeptide. In short: the animal data are real and interesting, the human data do not exist.
Pharmacokinetics
No human pharmacokinetic data for epithalon appear in the sources reviewed. Rat studies used both subcutaneous and oral administration; the oral studies measured enzyme activity in gut tissue rather than systemic exposure (Khavinson et al., 2002). As a free, unmodified tetrapeptide it is expected to be hydrolysed rapidly by peptidases, and a defined half-life in humans has not been reported.
Regulatory status as of September 2026
Epithalon is not approved as a medicine in the United States, Canada or the European Union, and has no registered clinical trial anywhere. It is sold online as a research chemical and as an ingredient in unregulated “longevity” products; such material is unlicensed and of unverified content, and marketing it for human use is illegal in those jurisdictions.
Epithalon vs pinealon vs vilon
The three best-known Khavinson peptides differ by sequence and by which claims dominate: epithalon (AEDG) carries the lifespan, tumour and telomerase literature; pinealon (EDR) the hypoxia and neuronal-viability work; vilon (KE) immune and gut-enzyme studies, sometimes combined with epithalon (Anisimov et al., 2002; Khavinson et al., 2002). All share the same origin, the same in-vitro DNA-binding hypothesis and the same absence of controlled human trials. The pinealon profile covers that peptide's evidence.
Sequence
One-letter sequence commonly cited for Epithalon (educational; isoforms and modifications may differ):
AEDG
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Linear tetrapeptide Ala-Glu-Asp-Gly (AEDG); free termini
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- PubChem molecular record · 2026-10-01
- Molecular formula
- C14H22N4O9
- Average reference mass
- ≈ 390.35
- Backbone
- Linear tetrapeptide Ala-Glu-Asp-Gly (AEDG); free termini
- Status
- Not approved anywhere; no trials registered on ClinicalTrials.gov (snapshot September 2026)
- PubChem CID: 219042
- CAS RN: 307297-39-8
- UNII: O65P17785G
Chemistry values: curated profile, PubChem · fetched 2026-10-01.
Epithalon — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Linear tetrapeptide Ala-Glu-Asp-Gly (AEDG); free terminiAverage reference mass: 390.35 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Epithalon
What is Epithalon?+
Epithalon (epitalon) is the synthetic tetrapeptide Ala-Glu-Asp-Gly (AEDG), designed from the amino-acid composition of epithalamin, a bovine pineal extract. Twenty-five years of mostly Russian cell and animal studies report lifespan extension in mice, telomerase induction in cultured fibroblasts and effects on melatonin and gene expression; there is no controlled human trial and it is not an approved medicine.
What Canadian product status is recorded for Epithalon?+
Canadian product status for Epithalon has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Epithalon?+
Epithalon is commonly described as approximately 4 amino acids (Research peptide).
What is epithalon?+
The synthetic tetrapeptide Ala-Glu-Asp-Gly (AEDG), designed from the amino-acid composition of a bovine pineal extract. It is a research compound with animal and cell-culture data and no controlled human trial.
Does epithalon lengthen telomeres?+
One 2003 cell-culture study reported telomerase induction and telomere elongation in human fetal fibroblasts. No human study has measured this after taking epithalon.
Did epithalon extend lifespan?+
In HER-2/neu transgenic mice, average lifespan rose 13.5% and maximum 13.9% (Anisimov et al., 2002). There are no human lifespan data.
Is epithalon approved?+
No. It is not an approved medicine in the US, Canada or the EU and has no registered clinical trial.
What are epithalon's side effects?+
Unknown in humans: no controlled safety study exists. The animal studies did not report systematic toxicity data in their abstracts.
Epithalon vs pinealon?+
Same research programme, different sequences and claims. Epithalon has the lifespan and telomerase studies; pinealon the hypoxia and neuronal work. Neither has a randomised human trial.
Further reading
- FoundationsWhat Are Research Peptides? A Clear Educational GuideLearn what “research peptides” means, how they differ from approved peptide drugs, quality markers (COA, purity), and how to study them responsibly.
- SafetyPeptide Safety and Risks: A Balanced Educational OverviewAn objective, balanced overview of what research does and does not establish about peptide risks—unknowns, purity and contamination concerns, and why unapproved compounds carry uncertainty. Not reassurance and not medical advice.
- PK conceptsWhy Peptides Have Short Half-Lives (And How Engineers Fix It)Proteases, renal clearance, DPP-4, PEGylation, lipidation, cyclization—educational guide to peptide pharmacokinetics concepts.
- Not a peptideIs NAD+ a Peptide? No — It Is a Coenzyme. What NAD+, NMN and NR Actually Are and What the Evidence Shows“NAD+ peptide” is a search term with no molecule behind it: NAD+ is a nucleotide coenzyme, not a peptide. This guide explains what NAD+ is, why it appears in peptide catalogues, what the precursors NMN and NR do, what human trials have and have not shown, and the regulatory status of each.
Related peptides
References & further reading
- 1.Anisimov et al. (2002). Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice. Bull Exp Biol Med
- 2.Khavinson et al. (2001). Modulating effects of epithalamin and epithalon on the functional morphology of the spleen in old pinealectomized rats. Bull Exp Biol Med
- 3.Anisimov et al. (2002). Studies of the effects of Vilon and Epithalon on gene expression in mouse heart using DNA-microarray technology. Bull Exp Biol Med
- 4.Anisimov et al. (2002). Epithalon inhibits tumor growth and expression of HER-2/neu oncogene in breast tumors in transgenic mice characterized by accelerated aging. Bull Exp Biol Med
- 5.Al-Dulaimi et al. (2025). Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology
- 6.Gatta et al. (2025). The Antioxidant Tetrapeptide Epitalon Enhances Delayed Wound Healing in an in Vitro Model of Diabetic Retinopathy. Stem Cell Rev Rep
- 7.Yue et al. (2022). Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro. Aging (Albany NY)
- 8.Kossoy et al. (2006). Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo
- 9.Araj et al. (2025). Overview of Epitalon — highly bioactive pineal tetrapeptide with promising properties. International Journal of Molecular Sciences
- 10.Khavinson et al. (2003). Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bulletin of Experimental Biology and Medicine
- 11.Khavinson & Golubev (2002). Aging of the pineal gland. Advances in Gerontology
- 12.Fedoreyeva et al. (2011). Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA. Biochemistry (Moscow)
- 13.Khavinson et al. (2003). Retinoprotective effect of Epithalon in Campbell rats of various ages. Bulletin of Experimental Biology and Medicine
- 14.PubChem — Epitalon, CID 219042