Epitalon Peptide: Telomerase Evidence, 10mg vs 50mg and Spray vs Vial

Epitalon peptide: telomerase evidence, 10mg vs 50mg, and spray vs vial

Epitalon is a synthetic four-amino-acid peptide (AEDG) studied for one striking laboratory finding: in human cell cultures it was reported to switch on telomerase and lengthen telomeres. This research-use-only reference explains what Epitalon is, what the cell-culture and animal data show, its pineal-gland origin, how the 10mg and 50mg vials, the nasal spray and the pen differ, what the published studies measured, and why the human longevity question stays open.

What is Epitalon peptide?

Epitalon is four residues long: alanine, glutamate, aspartate, glycine. Its formula is C14H22N4O9 and its calculated molecular weight is 390.35 g/mol for the free acid, one of the smallest compounds in any peptide catalogue. Two of the four residues are acidic and none is basic, so at neutral pH the molecule carries a net charge of about -2. It has no aromatic residue, so it does not absorb at 280 nm and its concentration cannot be checked that way. With no cysteine, methionine, tryptophan or asparagine it has few oxidation-prone sites; its main weak point is the aspartate-glycine pair at positions 3 and 4, discussed under storage.

Two spellings circulate. Epitalon and Epithalon (occasionally Epithalone) refer to the same tetrapeptide; the variation is transliteration from Russian, not chemistry. AEDG, the single-letter sequence, is the least ambiguous name of the three, and the literature should be searched under all of them because the spellings fragment the record.

The compound belongs to the family of short peptides developed at the St Petersburg Institute of Bioregulation and Gerontology under Vladimir Khavinson, usually called bioregulators. The family shares sequence fragments: Chonluten is Glu-Asp-Gly, which is Epitalon minus its alanine; Pinealon is Glu-Asp-Arg; Vilon is Lys-Glu; Thymogen is Glu-Trp. The programme's working hypothesis is that these short acidic peptides enter the nucleus and interact with DNA in a sequence-dependent way, modulating tissue-specific gene expression. That mechanism has not been established outside the programme and is best read as a hypothesis.

From epithalamin to Epitalon: the pineal connection

The pineal gland makes melatonin and sets the night-time rhythm of its secretion. That rhythm flattens with age: the evening rise becomes smaller and later, one of the more reproducible markers of neuroendocrine ageing. In the 1970s and 1980s, Khavinson and Morozov prepared a polypeptide extract from bovine pineal glands, named it epithalamin, and reported that it restored aspects of pineal function in old animals and extended their lifespan; their 2010 review puts the lifespan gain for the peptide preparations as a class at 20 to 40% in rodents. An extract has batch variability and an undefined composition. Epitalon was designed later as a defined synthetic substitute, a tetrapeptide whose sequence was chosen from the amino-acid composition of epithalamin.

The best-known test of that design is in primates. Khavinson, Goncharova and Lapin reported in 2001 that in aged female rhesus monkeys, whose evening melatonin rise had been lost, Epitalon significantly stimulated evening melatonin synthesis and normalised the circadian rhythm of cortisol secretion. A 2005 paper from the same collaboration reported that Epitalon lowered basal glucose and insulin, raised night-time melatonin and normalised the insulin response to a glucose load in monkeys aged 20 to 27, without affecting young animals. In elderly people the group reported that both epithalamin and Epitalon restored night-time melatonin release and normalised its daily rhythm (Korkushko and colleagues, 2007). These are small studies from one programme, but the melatonin result is the part of the Epitalon story with the most consistent support across species.

Does Epitalon activate telomerase?

This is the claim that made Epitalon famous, and it rests on a short report. Khavinson, Bondarev and Butyugov published in the Bulletin of Experimental Biology and Medicine in 2003 that adding Epitalon to cultures of human fetal fibroblasts induced expression of the telomerase catalytic subunit, produced detectable telomerase enzymatic activity, and lengthened telomeres in cultures that had been telomerase-negative. A 2004 follow-up from the same authors reported that fetal pulmonary fibroblasts which stopped dividing at passage 34 went on to 44 passages after Epitalon was added, ten extra divisions, with telomeres restored to their early-passage length. Related papers from the group reported that Epitalon activated ribosomal genes and decondensed pericentromeric heterochromatin in cultured lymphocytes from people aged 76 to 80 (Khavinson and colleagues, 2003), that fluorescently labelled short peptides including AEDG entered the nucleus of HeLa cells and bound DNA in vitro (Fedoreyeva and colleagues, 2011), and that molecular modelling could place AEDG in the DNA major groove at particular sequences (Khavinson and colleagues, 2013).

Three things about this evidence should be stated plainly.

• The original telomerase and telomere results came from the originating group, and the 2003 paper is a short communication in a translated Russian journal, with the limited methods detail that format allows. That single-source position changed in 2025. Al-Dulaimi and colleagues at Brunel University London, a laboratory with no connection to the St Petersburg programme, reported dose-dependent telomere lengthening in normal human epithelial and fibroblast cells treated with 0.1 to 1 µg/mL of Epitalon, together with higher hTERT mRNA and higher telomerase activity. The paper carries a published correction, and its authors note that the rise in telomerase activity in normal cells stays well below the levels seen in cancer lines.
• Telomerase activation in a normal somatic cell is not self-evidently good. Reactivation of the telomerase catalytic subunit is a feature of most human cancers, so a compound that switched it on in ordinary cells would need careful tumour-safety work. The group's own mouse studies report fewer tumours rather than more, which is either reassuring or a sign that the cell-culture effect does not carry over into animals. In the 2025 Brunel work the two breast cancer lines lengthened their telomeres through alternative lengthening of telomeres rather than through telomerase, so the peptide acted on cancer cells by a different route than on normal ones.
• Telomere lengthening in a dish, if real, is not lifespan extension in an organism. The animal work below is the only place that question has been tested.

The honest summary is that the cell-culture telomerase finding has now been reproduced once outside the originating programme, in a single 2025 paper, while everything downstream of it, in animals and in people, still rests on the programme's own work. That is a reason to study the compound and a reason not to overstate it. Work on Epitalon from groups outside the programme has grown since 2022, covering oocyte ageing and retinal wound-healing models as well as the telomere study; a 2025 review from the Medical University of Warsaw summarises the field and is listed under References.

What the animal lifespan data show

The rodent studies were run by Vladimir Anisimov's laboratory at the Petrov Institute of Oncology in St Petersburg with Khavinson as co-author. They share a design: treatment started in young adulthood and continued for life, with survival, tumour incidence and ageing biomarkers as endpoints.

In female CBA mice (Mechanisms of Ageing and Development, 2001), Epitalon and the thymic dipeptide Vilon were tested side by side. Fifty mice were treated from 6 months of age until natural death. Epitalon was reported to slow the ageing of oestrous function, lower body temperature and free radical processes, reduce spontaneous tumour incidence (mainly lung adenomas), raise mean survival by 5.3% and extend maximum lifespan by 10 months. In female Swiss-derived SHR mice (Biogerontology, 2003), Epitalon given from the age of 3 months until natural death, with 54 animals per group, did not change mean lifespan but raised maximum lifespan by 12.3% and the lifespan of the last 10% of survivors by 13.3%, slowed the age-related switching off of oestrous function, and cut chromosome aberrations in bone marrow cells by 17.1%. Total spontaneous tumour incidence was unchanged in this study, though leukaemia was six times less frequent. In HER-2/neu transgenic mice, which develop mammary tumours spontaneously (International Journal of Cancer, 2002), Epitalon given from 2 months of age reduced the cumulative number and maximum size of mammary tumours and lowered HER-2/neu mRNA expression 3.7-fold. In female rats kept under different lighting regimes (Vinogradova and colleagues, 2007), Epitalon given from 4 months of age did not change lifespan under a standard day and night cycle, but extended maximum lifespan by 95 days under natural northern light and by 24 days under constant light. Its effect on tumours was narrower than the lifespan result: tumour development was inhibited only in the rats under natural light, and was largely unaffected under standard and constant lighting.

Read together, the rodent work points the same way without being uniform: the clearest and most repeated signal is on the tail of the survival curve, maximum lifespan and the longest-lived tenth, while mean lifespan moved in one study out of three and the tumour findings differ by strain and by lighting condition. Read critically, every published mammalian lifespan study of Epitalon comes from this one collaboration, with modest group sizes, and the compound has not been through a multi-site programme such as the NIA Interventions Testing Program.

Male rats under three lighting regimes

Alongside the female rat study described above, the same collaboration ran a lighting experiment in male rats. Vinogradova and colleagues housed animals under a standard 12-hour light regime, under permanent light, or under the natural light of North-Western Russia (Vinogradova et al. 2008). Both permanent and natural light shortened survival compared with the standard regime, and permanent light also promoted spontaneous tumours (Vinogradova et al. 2008). With the animals followed until natural death, Epitalon hardly changed mean lifespan in any group (Vinogradova et al. 2008). It was associated with a significant normalisation of the population ageing rate, measured as the time for the mortality rate to double, in the rats kept under natural or permanent light (Vinogradova et al. 2008).

The tumour result differed from the female study. In males, Epitalon inhibited spontaneous tumours under every lighting regime, mainly testicular Leydig cell tumours and leukaemias (Vinogradova et al. 2008), whereas in females the effect was confined to natural light. The paper appeared in the Bulletin of Experimental Biology and Medicine and shares its first authors with the female study, so it adds a second sex and a second set of conditions to the rodent record without adding a new research group.

Human reports from the St Petersburg group

Most human data attached to Epitalon concern epithalamin, the extract. Khavinson and Morozov reported in 2003 on 266 elderly people followed for 6 to 8 years, with the peptide preparations given during the first 2 to 3 years. Mortality fell 1.6 to 1.8-fold in the epithalamin group and 2.5-fold in those given epithalamin together with thymalin, against the control group. Korkushko and colleagues at the Institute of Gerontology in Kyiv reported in 2011 on 39 elderly coronary patients with a rapidly ageing cardiovascular system who received epithalamin over three years alongside standard therapy, against 40 patients on standard therapy alone. Over a 15-year follow-up they reported slower cardiovascular ageing, better retained physical endurance, a normalised melatonin rhythm and lower mortality in the treated group. Both studies come from a single programme and used an extract of undefined composition rather than the synthetic tetrapeptide, so neither says anything about the synthetic tetrapeptide AEDG. The 2003 report was an open study; the 2011 report describes itself as a randomised comparative study, which makes it the stronger of the two by design, though it remains unreplicated.

Epitalon itself has been given to people in a few of the group's reports. Khavinson and colleagues described in 2002 that patients with retinitis pigmentosa who received a course of Epitalon showed a positive clinical effect in 90% of cases, alongside a parallel study in Campbell rats in which the peptide preserved retinal structure and raised the bioelectric activity of the retina. The melatonin rhythm work in elderly volunteers used both the extract and the synthetic peptide. None of these is a randomised, double-blind trial, and none measured telomere length or lifespan.

What research has not established

• Whether the telomerase result holds up beyond cell culture. One independent laboratory reproduced the cell-culture finding in 2025 with qPCR telomere measurement and telomerase activity assays, which is one replication rather than a body of evidence. The proposed DNA-binding mechanism is still single-source, and the authors of the 2025 paper call for 3D culture and animal models before the compound is treated as an established anti-ageing agent.
• Any effect on human telomeres or human lifespan. No trial has measured either. The long-term mortality reports used the extract, not the peptide, and were not randomised.
• Intranasal absorption. The published Epitalon studies used injection in the animal and human work and culture medium in the cell work, and PrymaLab has not located one that used the nasal route. What fraction of a 390 Da acidic peptide crosses the nasal epithelium has not been measured for this compound. The general question is covered in Do peptide nasal sprays work?
• Regulatory status. Epitalon has no approved human or veterinary formulation in any jurisdiction. Everything on this page is for research use only.

Epitalon 10mg vs 50mg

The two vials hold the same lyophilised tetrapeptide. The choice is about quantity, openings and arithmetic, and on a molecule this small the arithmetic has one feature worth knowing before either is opened.

The feature worth knowing is net peptide content. Epitalon has two acidic side chains and a free amino terminus, so it can be supplied as a salt, and at 390 Da a counter-ion would be a large fraction of the mass. The free acid is 390.35; a disodium salt is near 434; a trifluoroacetate salt would add about 114 per site, which is why a mass near 500 on a certificate for a tetrapeptide is worth querying. Residual water after lyophilisation adds several percent more, so a nominal 10 mg vial of a salt form with typical moisture can contain closer to 8 mg of actual tetrapeptide. The label states the fill, not the peptide content, and a concentration calculated from the nominal fill will be high by that margin every time. Where a certificate reports net peptide content, that figure removes the error. PrymaLab's Epitalon certificates give the free acid and do not report net peptide content.

A scale note that follows from the literature. The published rodent studies used microgram amounts per animal, so the 50mg vial exists for cell-culture stock series and larger animal cohorts rather than because any published study needed tens of milligrams.

Epitalon nasal spray vs vial

A lyophilised vial and the nasal spray hold the same molecule under conditions that differ in one respect that matters: water.

Dry powder is chemically quiet. With no cysteine, methionine, tryptophan or asparagine-glycine motif, a sealed dry solid at refrigerator temperature has few ways to degrade. Water changes that. Peptide bonds hydrolyse slowly in solution, and aspartate followed by glycine at positions 3 and 4 is one of the more labile arrangements in peptide chemistry: the backbone nitrogen of the glycine attacks the aspartate side chain, closes a succinimide ring, and the ring reopens to give isoaspartate, in which the chain runs through the former side chain. The product has the same formula and mass as the parent, so a mass spectrometry identity check cannot see it and routine chromatography is not guaranteed to separate it. For a solution product, the fill date and storage temperature carry more information than the identity check.

The glycine terminus adds a second point specific to the spray. Carboxypeptidases work inward from the carboxy end and need to fit the terminal residue into an active site; glycine, with no side chain, slides in without obstruction, whereas proline-terminated relatives such as Cortagen and Prostamax obstruct that class of enzyme. A spray keeps the molecule in water where any contaminating enzyme activity can act, so sterility and clean handling matter more here than for the proline-terminated members of the family. What the spray changes about biology, as opposed to chemistry, is unmeasured: nasal absorption of AEDG has not been reported.

What the published studies measured

The table lists what published studies examined, in what model, and what they reported. Each finding is taken from the primary paper named in the row, and the epithalamin rows describe the extract, not the synthetic peptide.

Two cautions on reading the table. Rodent results have no validated translation to any other species. And the human rows describe an extract of unknown composition, so they say nothing about the synthetic tetrapeptide.

Storage and reconstitution

Lyophilised Epitalon is stored at -20°C, as the certificate states, protected from light and moisture. Light protection is good practice rather than a mechanistic need, since the molecule has no aromatic residue; moisture protection matters more, because water starts the aspartate-glycine chemistry described above. Bring a cold vial to room temperature before opening so condensation does not land on the powder, and record the date and number of openings, since a vial opened repeatedly carries more water.

Concentration is mass divided by volume: 10 mg dissolved in 2.0 mL of a suitable diluent is 5 mg/mL, and 50 mg in 5.0 mL is 10 mg/mL. Diluent is run down the inside wall and the vial is swirled, not shaken. If the certificate gives net peptide content, multiply the nominal fill by that fraction before calculating concentration; on a 390 Da peptide the correction can be ten percent or more.

Once in solution, Epitalon is a different article from the dry powder. The Asp-Gly isomerisation product weighs exactly what the parent weighs and accumulates fastest near neutral pH, so time in solution is the variable to control. Reconstituted vials are kept at 2-8°C and used within a short window; if a solution must be held longer, aliquot it and freeze the aliquots once rather than warming and chilling one vial repeatedly. The spray and the pen are formulated solutions and are stored at 2-8°C without freezing, as their product pages state.

Frequently asked questions

Key takeaways

• Epitalon (Epithalon, AEDG) is the synthetic tetrapeptide Ala-Glu-Asp-Gly, 390.35 Da, designed by the Khavinson group as a defined analogue of the pineal extract epithalamin.
• The telomerase claim began with a 2003 cell-culture report from the originating group and was reproduced once outside it, by a Brunel University London laboratory in 2025; no human study has measured telomere length after Epitalon.
• Rodent lifespan studies, all from one collaboration, reported their clearest effects on maximum lifespan and on the longest-lived tenth rather than on mean lifespan. The melatonin-rhythm result in aged monkeys and elderly people is the most consistently supported finding.
• The 10mg and 50mg vials hold the same lyophilised peptide; the nasal spray and the 15mg pen are solutions, in which the Asp-Gly pair slowly isomerises to a product of identical mass, so fill date and time in solution matter.
• Store lyophilised vials at -20°C and the spray and pen at 2-8°C without freezing. Where a certificate reports net peptide content, correct concentrations for it; on a 390 Da peptide the difference can be ten percent or more.

Related products

• Epitalon 10mg
• Epitalon 50mg
• Epitalon 10mg Nasal Spray
• Preloaded Autoinjector | Epithalon | 3ml Pen | 15mg
• Pinealon 10mg
• Thymalin 10mg
• Pinealon 20 mg
• Preloaded Pinealon pen (3 ml autoinjector, 6 mg)

Related reading

• FOXO4-DRI: senolytic evidence, mechanism and human trials
• SS-31 (elamipretide): what it is and research
• Peptide bioregulators by organ system

References

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. PubMed
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. PubMed
3. Khavinson V, Lezhava T, Monaselidze J, et al. Peptide Epitalon activates chromatin at the old age. Neuro Endocrinol Lett. 2003;24(5):329-333. PubMed
4. Fedoreyeva LI, Kireev II, Khavinson VKh, Vanyushin BF. 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). 2011;76(11):1210-1219. PubMed
5. Khavinson V, Tarnovskaya S, Linkova N, et al. Short cell-penetrating peptides: a model of interactions with gene promoter sites. Bull Exp Biol Med. 2013;154(3):403-410. PubMed
6. Anisimov VN, Khavinson VKh, 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. PubMed
7. Anisimov VN, Khavinson VKh, Popovich IG, et al. Effect of Epitalon on biomarkers of ageing, life span and spontaneous tumour incidence in female Swiss-derived SHR mice. Biogerontology. 2003;4(4):193-202. PubMed
8. Anisimov VN, Khavinson VKh, 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. PubMed
9. Vinogradova IA, Bukalev AV, Zabezhinski MA, Semenchenko AV, Khavinson VKh, Anisimov VN. Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes. Bull Exp Biol Med. 2007;144(6):825-830. PubMed
10. Khavinson V, Goncharova N, Lapin B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro Endocrinol Lett. 2001;22(4):251-254. PubMed
11. Goncharova ND, Vengerin AA, Khavinson VKh, Lapin BA. Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas. Exp Gerontol. 2005;40(1-2):51-57. PubMed
12. Khavinson V, Razumovsky M, Trofimova S, et al. Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa. Neuro Endocrinol Lett. 2002;23(4):365-368. PubMed
13. Korkushko OV, Lapin BA, Goncharova ND, et al. Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people. Adv Gerontol. 2007;20(1):74-85. PubMed
14. Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuro Endocrinol Lett. 2003;24(3-4):233-240. PubMed
15. Korkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA. 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. The preparation studied was epithalamin. PubMed
16. Araj SK, Brzezik J, Madra-Gackowska K, Szeleszczuk L. Overview of Epitalon, a highly bioactive pineal tetrapeptide with promising properties. Int J Mol Sci. 2025;26(6):2691. PubMed
17. 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. PubMed. Correction: Biogerontology. 2025;27(1):1. PubMed
18. Anisimov VN, Khavinson VKh. Peptide bioregulation of aging: results and prospects. Biogerontology. 2010;11(2):139-149. PubMed