Epitalon Research, Specifications & Scientific Information

Introduction

Epitalon is four amino acids long — Ala-Glu-Asp-Gly, 390 daltons — which makes it one of the smallest molecules with a research literature of its own. It was not discovered in tissue and then synthesised. It was constructed the other way round: from the amino acid composition of Epithalamin, a bovine pineal gland extract, and only later identified inside the pineal polypeptide complex by mass spectrometry ^[10].

The claims attached to it are unusually large for a molecule this small, and the evidence behind them is unusually concentrated. Nearly all of the primary work comes from one group in St Petersburg and its collaborators, much of it published in one journal. The telomerase findings that dominate discussion of this compound are cell-culture results in a fetal fibroblast line, from that group, unreplicated elsewhere ^{[3, 8]}. The long-term human mortality data usually cited alongside them are not about this compound at all — they are about the extract ^{[5, 9]}.

This page separates those things.

What Is Epitalon?

Epitalon — also written Epithalon and Epithalone — is a synthetic tetrapeptide, AEDG in single-letter code, with free termini and no modification. It belongs to the series of short peptides developed by Vladimir Khavinson's group and usually called peptide bioregulators: molecules designed from the amino-acid composition of tissue-specific polypeptide extracts, on the premise that a short sequence can reproduce the activity of the complex it came from.

That premise is stated explicitly in the group's own work. A 2017 paper reports that the pineal polypeptide complex contains free amino acids, dipeptides, tripeptides and tetrapeptides; that AEDG was detected among the tetrapeptides by selective reaction monitoring; and concludes that the biological effects of the complex are determined by the effect of its component AEDG ^[10]. The detection is an analytical result. The conclusion drawn from it — that one component accounts for the activity of the whole mixture — is an inference, and a strong one.

Epitalon has not been approved by the U.S. Food and Drug Administration for any indication. No marketing application for it is on record in the United States, and no study of it is registered on ClinicalTrials.gov. Pineal preparations sold under other names in other jurisdictions are extracts or polypeptide complexes, which are different substances from a single synthetic tetrapeptide.

Epitalon Specifications

Epitalon is a linear tetrapeptide with free N- and C-termini and no modification of any kind. It was designed from the amino acid composition of Epithalamin, a bovine pineal gland extract, rather than from a known endogenous sequence; the tetrapeptide was subsequently identified within the pineal polypeptide complex itself by selective reaction monitoring mass spectrometry. At 390.35 g/mol it is among the smallest compounds carried in this library, and three of its four residues carry ionisable side chains or termini — glutamate and aspartate contribute two carboxylates on top of the C-terminal one — so the molecule is strongly acidic and highly water-soluble. A peptide this short and this polar poses analytical questions that larger peptides do not: it is poorly retained on conventional reversed-phase columns, it has no aromatic residue and therefore no useful absorbance at 280 nm, and its mass falls in the region where matrix and buffer signals are dense. The identifiers here are the records held by PubChem (CID 219042), which carries CAS registry number 307297-39-8 and FDA/NCATS UNII code O65P17785G. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Epitalon Work?

The proposed mechanism is not receptor pharmacology. It is a proposal that the peptide acts on gene transcription directly.

The reasoning runs as follows. A tetrapeptide is too small to present the kind of surface that receptor binding normally requires, and no receptor for it has ever been sought successfully. What the originating group proposed instead is that regulatory oligopeptides of this class initiate transcription of specific genes by binding their promoter regions, and they identified candidate nucleotide-pair binding sites in the promoters of retinal gene F379, of telomerase, and of RNA polymerase II ^[6]. Later work extended the proposal to chromatin: molecular modelling described preferential binding to histone H1/6 and H1/3 at specific peptide motifs that interact with DNA ^[11].

Three things should be said about that account. It is internally coherent and it makes testable predictions. It rests on computational modelling and on expression measurements rather than on direct structural determination of a peptide–DNA or peptide–histone complex. And a 2025 review written outside the originating group — by pharmaceutical scientists in Warsaw and Toruń — concludes that despite the considerable volume of biological and pharmacodynamic work, the quantity of physico-chemical and structural investigation of this peptide remains quite limited, and that it is uncertain whether the described effects are the only mechanisms ^[12].

A separate and more basic question is unanswered in the accessible literature: how a 390-dalton peptide carrying three carboxylate groups reaches the nucleus of a cell, or survives in plasma long enough to reach a cell at all. No pharmacokinetic dataset is published.

Epitalon Mechanism of Action

In vitro research

Telomerase in fetal fibroblasts. Adding the peptide to a culture of telomerase-negative human fetal fibroblasts induced expression of the telomerase catalytic subunit, enzymatic telomerase activity, and telomere elongation. The authors interpreted this as reactivation of the telomerase gene in somatic cells ^[3].

Proliferative lifespan in culture. In a follow-up, primary pulmonary fibroblasts derived from a 24-week fetus lost proliferative potential at passage 34, with mean telomere size appreciably below that at passage 10. Adding the peptide to the ageing culture elongated telomeres to a length comparable with early passages, and the treated cells made ten further divisions — to passage 44 — and continued dividing. The authors describe this as overcoming the Hayflick limit ^[8].

These are the two results the compound is known for, and they should be read with their limits attached. Both come from the same three-author group. Both are short reports — three and four pages — in Bulletin of Experimental Biology and Medicine. Neither has been independently replicated in the indexed literature in the two decades since. And the claim itself is a strong one: telomerase reactivation in normal human somatic cells, if reproducible, would be a significant result in cell biology, and significant results attract replication. The absence of replication here is information.

Neurogenic differentiation markers. In human gingival mesenchymal stem cells, the peptide raised protein levels of four neurogenic differentiation markers — nestin, GAP43, beta-tubulin III and doublecortin — and raised their messenger RNA expression by 1.6- to 1.8-fold. In the same paper, molecular modelling described peptide binding to histone H1/6 and H1/3 at the sequences His-Pro-Ser-Tyr-Met-Ala-His-Pro-Ala-Arg-Lys and Tyr-Arg-Lys-Thr-Gln, which interact with DNA ^[11].

This study is a collaboration between the originating group and an Italian university department, which makes it the closest thing in the set to external corroboration — though the peptide, the hypothesis and the senior authorship are still the originating group's.

Computational identification of binding sites. Promoter-region sequences capable of serving as binding sites for the tetrapeptide were identified in the genes for retinal protein F379, telomerase and RNA polymerase II ^[6]. A sequence that can bind is not a sequence that does bind, and the paper is explicit that it proceeds from a hypothesis.

Findings in this section were obtained in cell culture and by computation. Nothing in them establishes anything about intact animals or about humans.

What Is Epitalon Being Researched For?

• Telomere maintenance in cultured human cells — the telomerase and Hayflick-limit work ^{[3, 8]}.
• Geroprotection in rodents — lifespan, maximum lifespan, oestrous function, chromosome aberrations and spontaneous tumour incidence in mice ^[4].
• Retinal degeneration — hereditary pigmentary dystrophy in Campbell rats ^[1] and a clinical observation in degenerative retinal disease ^[2].
• Neuronal differentiation of human stem cells — expression and protein synthesis of neurogenic markers ^[11].
• Pineal and melatonin biology — chiefly through the extract rather than the tetrapeptide ^[7].
• Analytical chemistry of pineal polypeptide complexes — identification of the tetrapeptide within the complex ^[10].

None of that is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Epitalon

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

There is one indexed human report on the tetrapeptide itself, and it is thin.

Degenerative retinal disease, 2002

Design. A single paper in Neuro Endocrinology Letters reporting both animal and clinical work: the effect of the tetrapeptide on congenital pigmented degeneration of the retina in Campbell rats, followed by a clinical observation in people with degenerative retinal lesions ^[2].

Result as reported. In rats, intensified bioelectric and functional activity of the retina attributed to preservation of morphological structure. In humans, "a positive clinical effect in 90% of the cases" ^[2].

Limitations. The indexed abstract gives no participant count, no control group, no randomisation, no blinding, no endpoint definition and no measure of effect beyond the 90% figure — which is a proportion of an unstated denominator assessed by unstated criteria. It is indexed as a clinical trial, but nothing in the available record supports treating it as controlled evidence. An uncontrolled response proportion in a degenerative eye condition, judged by the investigators who proposed the compound, is the weakest form a clinical claim comes in.

That is the whole of the directly indexed human literature on this tetrapeptide. Everything else in the human record belongs to the extract, and is described in a separate section below rather than here, because the distinction is the single most commonly collapsed point about this compound.

Preclinical Research on Epitalon

Animal research

The rodent work is the most rigorously designed material on this compound, and its results are more specific — and more modest — than the summaries usually suggest.

Lifespan and tumour incidence in mice

Female outbred Swiss-derived SHR mice were injected subcutaneously on five consecutive days each month from the age of three months until natural death, with either saline or 1.0 µg per mouse of the peptide. There were 54 animals in each group ^[4].

What the peptide did not change: food consumption, body weight, mean lifespan, or total spontaneous tumour incidence.

What it did change: the age-related switching-off of oestrous function slowed; the frequency of chromosome aberrations in bone marrow cells fell by 17.1% (p < 0.05); the lifespan of the last 10% of survivors rose by 13.3% (p < 0.01); maximum lifespan rose by 12.3%; and the development of leukaemia was inhibited 6.0-fold against control ^[4].

The authors' own conclusion is carefully worded — that the data suggest geroprotector activity and the safety of long-term administration in mice — and the distinction between mean and maximum lifespan carries most of the weight. A compound that leaves mean lifespan untouched while extending the tail of the survival curve is doing something different from one that makes a population healthier on average, and the 6-fold reduction in leukaemia against unchanged total tumour incidence is a redistribution rather than a reduction of cancer.

Retinal degeneration in Campbell rats

Administration from birth in rats with hereditary pigmentary retinal degeneration was reported to protect morphological structure, increase bioelectrical activity and improve retinal function ^[1]. The indexed abstract carries no group sizes and no numerical results, so nothing quantitative is stated here from it.

Findings described in this section were observed in mice and rats. Nothing in them establishes anything about humans.

Other Areas of Epitalon Research

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

This section exists to set out, and keep separate, the human literature on Epithalamin — the bovine pineal gland extract from which the tetrapeptide's composition was derived. It is routinely cited as though it were evidence about the tetrapeptide. It is not: an extract is a mixture, and the tetrapeptide is one identified component of it ^[10].

Circadian melatonin in elderly subjects. Plasma melatonin rhythm was studied in healthy elderly participants before and after a course of the extract. The reported effect was modulation rather than elevation: during the dark period plasma melatonin rose in participants whose pineal activity was initially low, while in those with normal function it tended to fall ^[7]. A bidirectional result of that kind is interesting and is also difficult to distinguish from regression to the mean without a control group, which the indexed abstract does not describe.

Twelve-year randomised study in elderly subjects. Elderly participants with coronary disease and accelerated cardiovascular ageing received the extract over a twelve-year randomised clinical study. Reported outcomes: reduced functional age and degree of cardiovascular ageing, increased exercise tolerance, 28% fewer deaths than control at twelve years, twofold lower cardiovascular mortality, and twofold lower incidence of cardiovascular failure and respiratory disease ^[9].

Six-to-eight-year observation of two bioregulators. A separate report describes geroprotective assessment of thymic and pineal bioregulators in older people over six to eight years, with the preparations applied only during the first two to three years. Reported mortality reductions were 2.0–2.1-fold for Thymalin, 1.6–1.8-fold for Epithalamin, 2.5-fold for the combination, and 4.1-fold in a group given the combination annually for six years ^[5].

Four cautions apply to all three, and they are substantial. The substance studied is the extract, not the tetrapeptide. The investigators are the compounds' originators. Mortality reductions of the size reported — up to 4.1-fold from a few courses of a peptide extract — are far larger than anything established medicine achieves in the same populations, which raises the evidentiary bar rather than lowering it. And none of this work has been replicated by an independent group, registered as a trial, or published in a journal outside the small set that carries this programme's output.

The 2025 independent review summarises the state of play fairly: twenty-five years of in vitro, in vivo and in silico study, with significant reported geroprotective and neuroendocrine effects, and open questions about mechanism and about the limited physico-chemical and structural work ^[12].

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Epitalon vs Related Compounds

Epitalon versus Epithalamin

The single most important distinction on this page. Epithalamin is a bovine pineal gland extract — a mixture of free amino acids, di-, tri- and tetrapeptides. Epitalon is a single synthetic tetrapeptide designed from that mixture's amino acid composition and later identified within it ^[10]. Human mortality and melatonin data attach to the extract ^{[5, 7, 9]}; they are not evidence about the tetrapeptide.

Within the bioregulator series

Thymalin and the other Khavinson preparations were designed the same way, each from a different tissue extract, on the same premise that a short sequence reproduces the activity of the complex. Vilon (Lys-Glu) and Pinealon (Glu-Asp-Arg) are the short synthetic members most often set beside this one. They share a research programme and a set of methodological limitations, not a mechanism.

N-acetyl Epitalon

An acetylated variant with its own identifiers and a much smaller literature. Nothing established for the unmodified tetrapeptide transfers to it automatically.

Against telomerase pharmacology generally

Compounds developed as telomerase activators in the wider literature are characterised with enzyme kinetics, cell-line panels and independent replication. The telomerase work on this tetrapeptide consists of two short reports from one group ^{[3, 8]}. The comparison is one of evidentiary weight, not of effect.

Regulatory position

Not approved by the U.S. Food and Drug Administration for any indication, with no registered trial anywhere.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

Epitalon is an unmodified four-residue peptide with free N- and C-termini. PubChem carries it as compound identifier 219042, with CAS registry number 307297-39-8 and FDA/NCATS UNII code O65P17785G. The recorded molecular formula is C14H22N4O9 and the average mass 390.35 g/mol.

Three carboxylates, no basic residue. Glutamate at position 2, aspartate at position 3 and the C-terminal glycine carboxyl give the molecule three ionisable acidic groups against a single N-terminal amine. It is therefore strongly acidic, highly water-soluble, and net negatively charged at physiological pH — properties that argue against passive membrane crossing and that sit awkwardly beside a proposed mechanism of action inside the nucleus.

No aromatic residue. There is no tryptophan, tyrosine or phenylalanine, so the peptide has essentially no absorbance at 280 nm. Ultraviolet quantification has to rely on peptide-bond absorbance near 214 nm, where buffers and solvents also absorb. This is a genuine analytical constraint and it applies to every lot of this material.

Poor reversed-phase retention. A 390-dalton peptide of this polarity is weakly retained on conventional C18 columns and can elute close to the void volume, where it is difficult to separate from salts and from synthesis-related impurities. A purity figure "by HPLC" is only as meaningful as the method behind it, and for this compound the method matters more than it does for a larger, more hydrophobic peptide.

Isomeric and sequence-related impurities. The glutamate and aspartate residues make this sequence susceptible to the same alpha/beta rearrangement chemistry that affects other Asp- and Glu-containing peptides, and the resulting isomers are identical in mass. Mass spectrometry confirms composition; it does not by itself confirm that the four residues are joined in the intended way through the intended bonds.

Those four points are the practical chemistry of this molecule, and they are not conveyed by a molecular formula or by a headline purity percentage.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Khavinson VKh, Razumovskii MI, Trofimova SV, et al.. Effect of epithalon on age-specific changes in the retina in rats with hereditary pigmentary dystrophy Bulletin of experimental biology and medicine; 2002. PMID 12170316 doi:10.1023/a:1015125031829
2. Khavinson V, Razumovsky M, Trofimova S, et al.. Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa Neuro endocrinology letters; 2002. PMID 12195242
3. Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells Bulletin of experimental biology and medicine; 2003. PMID 12937682 doi:10.1023/a:1025493705728
4. 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. PMID 14501183 doi:10.1023/a:1025114230714
5. Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life Neuro endocrinology letters; 2003. PMID 14523363
6. Khavinson VKh, Shataeva LK, Chernova AA. Effect of regulatory peptides on gene transcription Bulletin of experimental biology and medicine; 2003. PMID 14666197 doi:10.1023/b:bebm.0000008986.02891.de
7. Korkushko OV, Khavinson VKh, Shatilo VB, et al.. Effect of peptide preparation epithalamin on circadian rhythm of epiphyseal melatonin-producing function in elderly people Bulletin of experimental biology and medicine; 2004. PMID 15452611 doi:10.1023/b:bebm.0000035139.31138.bf
8. Khavinson VKh, Bondarev IE, Butyugov AA, et al.. Peptide promotes overcoming of the division limit in human somatic cell Bulletin of experimental biology and medicine; 2004. PMID 15455129 doi:10.1023/b:bebm.0000038164.49947.8c
9. Korkushko OV, Khavinson VKh, Shatilo VB, et al.. Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging Bulletin of experimental biology and medicine; 2006. PMID 17426848 doi:10.1007/s10517-006-0365-z
10. Khavinson VK, Kopylov AT, Vaskovsky BV, et al.. Identification of Peptide AEDG in the Polypeptide Complex of the Pineal Gland Bulletin of experimental biology and medicine; 2017. PMID 29124531 doi:10.1007/s10517-017-3922-8
11. Khavinson V, Diomede F, Mironova E, et al.. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism Molecules (Basel, Switzerland); 2020. PMID 32019204 doi:10.3390/molecules25030609
12. Araj SK, Brzezik J, Mądra-Gackowska K, et al.. Overview of Epitalon-Highly Bioactive Pineal Tetrapeptide with Promising Properties International journal of molecular sciences; 2025. PMID 40141333 doi:10.3390/ijms26062691

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: Epitalon specifications and lot documentation