Epitalon — also written Epithalon or Epithalone — is a synthetic tetrapeptide with the sequence Ala-Glu-Asp-Gly, developed in St Petersburg as a defined analogue of the pineal extract Epithalamin. This Epitalon research peptide guide covers its structure, the telomerase and pineal-signalling work that made it well known, an honest reading of the evidence base, and the handling data a laboratory needs. Everything here is written for research use only.
Key takeaways
- Epitalon is a four-residue peptide, Ala-Glu-Asp-Gly (AEDG), CAS 307297-39-8, formula C14H22N4O9, average molecular weight ≈390.35 Da.
- It was designed as a synthetic stand-in for Epithalamin, a bovine pineal peptide extract used in the Khavinson bioregulator programme — the two are related but not interchangeable in the literature.
- The best-known finding is a 2003 report by Khavinson and colleagues that Epitalon induced telomerase activity and telomere elongation in cultured human fetal fibroblasts.
- A 2003 lifespan study in female SHR mice reported no change in mean lifespan, but a 12.3% increase in maximum lifespan and fewer chromosome aberrations.
- Much of the supporting literature is small, single-centre, published in Russian-language or low-circulation journals, and rarely independently replicated — a 2025 review in IJMS makes the same point about structural characterisation.
- The peptide is highly polar and readily water-soluble; lyophilised material is stable frozen, while solutions are the fragile form.
- GenoPept supplies Epitalon as a lyophilised vial with a per-batch third-party certificate of analysis, strictly for laboratory research.
What is Epitalon (Epithalon)?
Epitalon is a synthetic tetrapeptide, Ala-Glu-Asp-Gly, created in the 1990s at the St Petersburg Institute of Bioregulation and Gerontology as a chemically defined analogue of the pineal peptide preparation Epithalamin. It belongs to the class of short “peptide bioregulators” associated with Professor Vladimir Khavinson, and it is studied in ageing, telomere and circadian biology models.
The spelling varies across the literature. Epitalon, Epithalon and Epithalone all refer to the same AEDG tetrapeptide, and papers translated from Russian frequently use “Epithalon”. Searching only one spelling will miss a large slice of the published record.
What makes the molecule unusual is its size. At four residues and under 400 daltons it is smaller than most signalling peptides — closer to a small molecule than to a protein fragment. That size is central to the hypothesis its originators proposed: that very short peptides can enter cells and nuclei and interact with regulatory DNA regions directly, rather than acting on a cell-surface receptor.
This guide is written for researchers, formulation chemists and purchasing staff who need the structural facts, a fair summary of what has and has not been demonstrated, and practical handling data. It is not a protocol for administration to any organism.
Structure, sequence and chemical specification
Epitalon is H-Ala-Glu-Asp-Gly-OH: a linear, unmodified, all-L tetrapeptide with a free N-terminal amine and a free C-terminal carboxyl, carrying two acidic side chains. There is no acylation, no amidation, no D-amino acid and no cyclisation — which is why it is one of the simplest peptides in the research catalogue to synthesise and to analyse.
Because there is no methionine or cysteine in the sequence, the classic oxidation pathway that degrades many peptides does not apply. The relevant chemistry instead sits at the aspartate–glycine junction, where Asp-Gly sequences are known to be prone to succinimide formation and subsequent isomerisation, particularly in solution at neutral-to-alkaline pH.
| Property | Value |
|---|---|
| Synonyms | Epithalon, Epithalone, AEDG peptide |
| Sequence (1-letter) | AEDG |
| Sequence (3-letter) | H-Ala-Glu-Asp-Gly-OH |
| Residues | 4 |
| CAS number | 307297-39-8 |
| Molecular formula | C14H22N4O9 |
| Average molecular weight | ≈390.35 g/mol |
| Modifications | None (free N- and C-termini, all-L) |
| Appearance as supplied | White to off-white lyophilised powder / cake |
| Solubility | Readily soluble in water and aqueous buffers |
| Typical QC methods | RP-HPLC purity, ESI-MS or MALDI-TOF identity |
Where Epitalon came from: Epithalamin and the Khavinson programme
Epitalon was developed as the synthetic successor to Epithalamin, a polypeptide extract of bovine pineal gland used in Soviet and post-Soviet gerontology research from the 1970s onward. The programme, led by Vladimir Khavinson, worked on the premise that organ extracts contain short regulatory peptides which could be identified and remade synthetically.
This distinction matters when reading the literature, and it is regularly blurred by secondary sources. Studies on Epithalamin used a complex, incompletely characterised extract. Studies on Epitalon used the defined AEDG tetrapeptide. A result obtained with one is not automatically a result for the other.
The most-cited human-cohort publication from this programme — Khavinson and Morozov’s 2003 report in Neuroendocrinology Letters, which followed 266 older participants over six to eight years and reported reduced mortality — used Thymalin and Epithalamin, the extracts, not synthetic Epitalon. That paper is frequently miscited as evidence for the tetrapeptide.
Within the wider bioregulator family, Epitalon is the pineal-associated member. Its siblings are covered in the Khavinson peptide bioregulators guide, which sets out the cytomax (extract) versus cytogen (synthetic short peptide) split in full.
Mechanisms reported in published research
Published work describes three main proposed mechanisms for Epitalon: induction of telomerase activity in cultured cells, restoration of pineal melatonin rhythm in aged animals, and direct modulation of gene expression through interaction with regulatory DNA. All three are hypotheses supported by specific experiments rather than settled pharmacology.
Telomerase induction in cell culture
The foundational report is Khavinson, Bondarev and Butyugov (2003) in Bulletin of Experimental Biology and Medicine. Working with telomerase-negative human fetal fibroblast cultures, the investigators reported that adding Epithalon induced expression of the telomerase catalytic subunit, measurable enzymatic activity and telomere elongation. A companion 2004 paper from the same group reported cultures exceeding the usual division limit.
These are in-vitro findings in a specific cell type from a single laboratory. They have not been widely reproduced by independent groups, which is the central caveat for anyone citing them.
Pineal and circadian signalling
A second strand of research examines the pineal gland. Reports in aged rodents and in primates describe Epitalon shifting melatonin secretion patterns back toward a younger profile, and modulating circadian clock-gene expression. The 2021 Molecules systematic review from the Khavinson group lists AEDG among peptides linked to neuro-immuno-endocrine and circadian gene activity.
Direct interaction with regulatory DNA
The mechanistic hypothesis the originators favour is that short peptides such as AEDG enter the nucleus and bind directly to promoter regions or to histones, altering chromatin accessibility. This model is set out across their publications, including the 2021 systematic review, and it is the unifying claim for the whole bioregulator class rather than something specific to Epitalon.
Independent structural and biophysical characterisation of this binding remains limited. The 2025 International Journal of Molecular Sciences review by Araj and colleagues, while broadly positive about the biological activity literature, states plainly that physico-chemical and structural investigation of the peptide is still quite limited and that it remains uncertain whether the described mechanisms are the only ones at work.
How strong is the Epitalon evidence base?
The honest summary is that Epitalon has an interesting but thin evidence base: a handful of in-vitro studies, several rodent lifespan and biomarker experiments, and almost no independent replication outside the originating research network. It is a legitimate research subject; it is not a well-characterised pharmacological agent.
Take the most-cited animal study. Anisimov, Khavinson and co-workers (2003, Biogerontology) followed groups of 54 female SHR mice. Epitalon did not change mean lifespan or body weight. It did increase maximum lifespan by 12.3%, extend survival of the final 10% of survivors by 13.3%, cut bone-marrow chromosome aberrations by roughly 17%, slow the age-related loss of oestrous function, and reduce leukaemia incidence six-fold without changing overall tumour incidence.
That is a mixed, specific result — and it is much more informative than the way it is usually paraphrased. Anyone citing Epitalon as “extending lifespan” is overstating what the paper reports.
| Claim frequently made | What the published work actually shows | Evidence tier |
|---|---|---|
| Activates telomerase | Induced hTERT expression and telomere elongation in cultured human fetal fibroblasts (2003) | In vitro, one laboratory |
| Extends lifespan | No change in mean lifespan in SHR mice; +12.3% maximum lifespan in the same study | Rodent, single study |
| Reduces cancer incidence | 6-fold fewer leukaemias in SHR mice; total tumour incidence unchanged | Rodent, single study |
| Improves genome stability | ~17% fewer bone-marrow chromosome aberrations in the same cohort | Rodent, single study |
| Restores melatonin rhythm | Reported in aged rodent and primate models; effect sizes vary between reports | Preclinical |
| Reduced mortality in older people | That 2003 cohort used the extracts Epithalamin and Thymalin — not synthetic Epitalon | Commonly miscited |
| Binds DNA directly | Proposed across the bioregulator literature; structural characterisation still limited (IJMS 2025) | Hypothesis |
Laboratory handling, solution preparation and storage
Lyophilised Epitalon is the stable form and should be kept frozen and dry; once it is in solution, the clock starts. The peptide dissolves readily in water or aqueous buffer, and its lack of Met and Cys removes the oxidation problem that complicates many other research peptides.
- Equilibrate before opening. Bring the sealed vial to room temperature before breaking the seal so that atmospheric moisture does not condense onto the cold cake.
- Choose a diluent. Sterile water or a suitable aqueous buffer is standard for assay work. Bacteriostatic water containing 0.9% benzyl alcohol is used where a multi-draw solution is wanted; see the bacteriostatic water guide.
- Add diluent slowly down the vial wall. Let it run onto the glass rather than jetting directly into the cake. Do not shake — swirl gently until clear.
- Inspect. The solution should be clear and colourless with no visible particulates or fibrils.
- Aliquot immediately. Split into single-use volumes so the stock is never repeatedly thawed. Freeze-thaw cycling is the most avoidable cause of loss.
- Label and log. Record compound, batch, concentration, diluent and preparation date on every aliquot.
| Peptide mass in vial | Diluent added | Resulting concentration | Amount per 0.1 mL | Approx. molar concentration |
|---|---|---|---|---|
| 10 mg | 1 mL | 10 mg/mL | 1000 mcg | ≈25.6 mM |
| 10 mg | 2 mL | 5 mg/mL | 500 mcg | ≈12.8 mM |
| 10 mg | 5 mL | 2 mg/mL | 200 mcg | ≈5.1 mM |
| 20 mg | 2 mL | 10 mg/mL | 1000 mcg | ≈25.6 mM |
| 20 mg | 4 mL | 5 mg/mL | 500 mcg | ≈12.8 mM |
| 50 mg | 5 mL | 10 mg/mL | 1000 mcg | ≈25.6 mM |
Molar figures use the free-peptide molecular weight of 390.35 Da and ignore salt and residual water, so treat them as upper bounds. Where exact molarity matters, use the net peptide content from the certificate of analysis.
General stability principles for short peptides are covered in more depth in the peptide storage guide, and step-by-step solution preparation in the reconstitution guide.
Epitalon compared with related longevity-research peptides
Epitalon sits in a group of short peptides studied in ageing biology, but its proposed mechanism is quite different from the mitochondrial peptides it is often listed alongside. Knowing which mechanism family a compound belongs to prevents a lot of confused experimental design.
Nuclear / gene-regulation family
Epitalon and the other Khavinson short peptides are proposed to act on transcription — entering the nucleus and altering gene accessibility. Effects, where reported, are slow and cumulative rather than acute.
Mitochondrial family
MOTS-c and SS-31 (elamipretide) act at the mitochondrion — AMPK signalling and cardiolipin binding respectively. Both have far more independent, peer-reviewed mechanistic literature than Epitalon does.
Practically, this means a researcher screening for bioenergetic readouts would not expect Epitalon to behave like a mitochondrial peptide, and a researcher looking at telomere or clock-gene endpoints would not expect SS-31 to behave like Epitalon. Match the compound to the assay.
Epitalon in the GenoPept store
Frequently asked questions
What is the difference between Epitalon and Epithalon?
There is no chemical difference. Epitalon, Epithalon and Epithalone are transliteration variants of the same synthetic tetrapeptide, Ala-Glu-Asp-Gly, CAS 307297-39-8. Russian-language papers and their translations tend to use “Epithalon”, while catalogue listings often use “Epitalon”. Searching both spellings is worthwhile because the published record is split across them.
Is Epitalon the same thing as Epithalamin?
No. Epithalamin is a polypeptide extract of bovine pineal gland — a complex, incompletely defined mixture used in earlier gerontology research. Epitalon is a single, chemically defined four-residue synthetic peptide developed as an analogue of it. Several widely quoted human-cohort findings were obtained with Epithalamin, not Epitalon, and the two should not be cited interchangeably.
What is the molecular weight and formula of Epitalon?
Epitalon has the molecular formula C14H22N4O9 and an average molecular weight of approximately 390.35 g/mol as the free peptide. Supplied material is normally a salt, so the actual peptide content per milligram of powder is lower than the label mass. Use the net peptide content figure on the certificate of analysis for molar calculations.
Does Epitalon really activate telomerase?
A 2003 study by Khavinson and colleagues reported that Epithalon induced telomerase catalytic subunit expression and telomere elongation in cultured human fetal fibroblasts. That result is in vitro, in one cell type, from one research group, and has not been broadly replicated independently. It is reasonable to describe it as a reported in-vitro finding, not as an established property.
Does Epitalon need to be refrigerated?
Sealed lyophilised material is best held frozen at −20 °C for long-term storage, with 2–8 °C acceptable as a working store. Once reconstituted, the solution should be refrigerated and used within a short window, or split into single-use aliquots and frozen. Repeated freeze-thaw cycling is the most common avoidable cause of loss in solution.
What is Epitalon soluble in?
Epitalon is highly polar, carrying two acidic side chains, and dissolves readily in water and standard aqueous buffers. Sterile water is typical for single-use assay solutions; bacteriostatic water with 0.9% benzyl alcohol is used where a multi-draw stock is wanted. Add diluent gently down the vial wall and swirl rather than shaking, then check for a clear, particulate-free solution.
How does Epitalon differ from MOTS-c and SS-31?
They belong to different mechanism families. Epitalon is proposed to act in the nucleus on gene expression. MOTS-c is a mitochondrial-DNA-encoded peptide studied through AMPK signalling and nuclear translocation. SS-31 (elamipretide) binds cardiolipin in the inner mitochondrial membrane. MOTS-c and SS-31 both have substantially more independent peer-reviewed mechanistic literature than Epitalon.
Why does a certificate of analysis matter for a peptide this small?
Short peptides are easy to synthesise, which makes deletion sequences and salt-loaded material easy to pass off. An HPLC trace confirms chromatographic purity and a mass spectrum confirms that the observed mass matches 390.35 Da for the free peptide. Without both, you cannot confirm you are working with AEDG rather than a truncated or substituted analogue.
References
- 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;135(6):590–592. DOI
- 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
- Araj SK, Brzezik J, Mądra-Gackowska K, Szeleszczuk Ł. Overview of Epitalon — highly bioactive pineal tetrapeptide with promising properties. International Journal of Molecular Sciences. 2025;26(6):2691. DOI
- Khavinson VKh, Popovich IG, Linkova NS, Mironova ES, Ilina AR. Peptide regulation of gene expression: a systematic review. Molecules. 2021;26(22):7053. DOI
- Anisimov VN, Khavinson VKh. Peptide bioregulation of aging: results and prospects. Biogerontology. 2010;11(2):139–149. DOI
- Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuroendocrinology Letters. 2003;24(3–4):233–240. Journal page
Research-grade Epitalon, batch-verified
GenoPept supplies Epitalon (Epithalon) as lyophilised vials with a per-batch third-party certificate of analysis covering HPLC purity and mass-spectrometry identity, dispatched from the UK, strictly for laboratory research.