Epithalon

Epithalon, also written Epitalon, is the synthetic tetrapeptide Ala-Glu-Asp-Gly.

Preclinical-heavyPeptide research profile

Also known as: Epitalon, AEDG

Sources reviewed October 1, 2026 (how we review)

Dosing & scaling, explained

The 1 mg daily for 10 days row is a recorded bioregulator convention, not a validated human longevity regimen. This is educational source context, not a protocol or recommendation.

How sourced amounts are organized

Starting pointNot clinically establishedNo validated titration window
There is no regulator-approved starting dose for this research use. A low-looking number is not automatically safe.
Recorded preset1 mg / dayCalculator library reference
This is the range represented in the in-app protocol library. It describes the source record; it does not validate the regimen.
Higher exposureNo validated upper exposureRisk and uncertainty increase
Higher exposure is not established as more effective. Human pharmacokinetic and long-term safety data may be absent.

Drug amount and device markings are different quantities. The calculator converts mass into volume, syringe units, or pen clicks.

Patterns described in source material

10-day block in the preset
The cadence represented by the recorded calculator presets.
Repeat every 4 months in the source row
Published experiments may use a different route, formulation, timing, or population and should not be treated as interchangeable.
No universal schedule
No single schedule has been validated across products or research contexts.

Clinical context

No regulator-grade human dose-ranging study establishes a schedule for telomere or longevity outcomes.

Storage, handling and interpretation

Lyophilized material

Keep cold, dry, and protected from light according to the manufacturer certificate or validated lab SOP.

After reconstitution

Use sterile technique, refrigerate as validated, and avoid repeated freeze-thaw cycles.

Traceability

Record lot, concentration, preparation date, and the identity/purity documentation used by the lab.

Reported protocols for Epithalon

What published studies and recent community write-ups report about amounts, timing and course length. 3 clinical, 6 preclinical and 4 community-reported rows, each linked to its source. These are descriptions of what others report, not instructions, and nothing here is medical advice.

Context	Dose	Frequency	Route	Course	Source
Clinical3 rows
Retinitis pigmentosa trial, injections beside the eye162 patients with retinitis pigmentosa aged 18-72, against a group given conventional 2002 care	5 mcg per eye	Once daily	Parabulbar injection, beside the eyeball	10 consecutive daysNone described	International Journal of Molecular Sciences (PubMed Central)2025
A 2025 review supplies the patient count, the per-eye dose and the 10-day course, reporting higher electroretinogram amplitudes, visual acuity up by 0.15-0.20 on average, wider visual fields in all patients and no side effects. The primary 2002 report's abstract gives no sample size, no randomisation and no description of the control group, and this remains the only publication on the compound that PubMed types as a clinical trial.
Sublingual spray in night-shift workers75 women aged 40-59 working night shifts; the 40 with reduced melatonin output were split between spray and saline placebo	0.5 mg per day (3 sprays twice daily)	Twice daily, morning and early afternoon	Sublingual spray	20 daysNone described	Advances in Gerontology (Springer)2021
Urinary 6-sulfatoxymelatonin excretion rose about 1.7-fold while the placebo group did not move, Clock and Csnk1e overexpression normalized by 1.9 to 2.1 fold and Cry2 underexpression doubled. The FDA's 2026 review notes that the study measured no sleep outcome at all, used the sublingual route rather than the subcutaneous route that was nominated, had a small sample and a short duration, and did not make clear whether it was blinded.
FDA review of the nominated subcutaneous productAdults; the nominated use evaluated was insomnia	10 mg/mL and 3,000 mcg/mL subcutaneous injections, as nominated	Not specified in the nominations	Subcutaneous, the nominated route	Not specified in the nominationsNot specified in the nominations	US Food and Drug Administration2026
FDA reported that no publication examines epitalon in patients with insomnia, that no nonclinical study measured behavioural or EEG sleep endpoints, that no pharmacokinetic data exist for either form, and that there are no studies at all using the proposed subcutaneous route. It judged both the free base and the acetate not well characterized, citing missing impurity, aggregation, bioburden and endotoxin data, and proposed that neither be added to the 503A Bulks List.
Preclinical6 rows
Lifelong monthly courses in SHR mice54 female outbred Swiss-derived SHR mice per group, from 3 months old to natural death	1 mcg per mouse, about 30-40 mcg/kg	5 consecutive days each month	Subcutaneous	Repeated monthly for lifeThe rest of each month with no dosing	Biogerontology (PubMed)2003
Food intake, body weight and mean life span did not change, but the last 10% of survivors lived 13.3% longer, maximum life span rose 12.3%, bone marrow chromosome aberrations fell 17.1% and the age-related loss of estrous function slowed. Total spontaneous tumour incidence was unchanged, although leukemia was recorded six-fold less often, and the whole study used one strain, one sex and one dose.
Transgenic HER-2/neu mice, five days a week for lifeFemale FVB/N transgenic mice carrying HER-2/neu, from the second month of life to death	1 mg as stated in this paper	5 times a week	Subcutaneous	Continuous until deathTwo days a week without dosing	Bulletin of Experimental Biology and Medicine (PubMed)2002
Average and maximum lifetime rose 13.5% and 13.9%, tumour-free lifetime rose 34.2%, lung metastases were 1.6-fold fewer, multiple tumours halved and HER-2/neu mRNA in mammary tumours was 3.7-fold lower. The stated 1 mg dose is a thousand times the 1 microgram per mouse used in companion papers on the same strain from the same programme, a discrepancy the literature does not resolve.
Female rats under three lighting regimesFemale rats kept under standard day and night, natural north-western Russian light, or constant light, from 4 months of age	0.1 mcg per rat	Daily, 5 times a week	Subcutaneous	Continuous from 4 months of ageTwo days a week without dosing	Bulletin of Experimental Biology and Medicine (PubMed)2007
Under a standard light and dark cycle the peptide did not change life span at all. Under natural northern light and constant light it extended maximum life span by 95 and 24 days, and it inhibited spontaneous tumour development only in the natural-light group, so the result depended entirely on the lighting the animals were housed under.
Ten-day course in old rhesus monkeysOld and young female rhesus monkeys	2 mcg/kg per day	Once daily	Intramuscular	10 daysNone described	US Food and Drug Administration2026
In the old animals evening serum melatonin rose and evening cortisol fell, with the young animals largely unaffected; this is the study most often cited for the compound's melatonin claim. The FDA's 2026 summary records that no dose-response relationship was tested and that neither sleep behaviour nor EEG activity was measured, so the effect on sleep is unknown.
Direct test on perifused rat pineal glandsPineal glands from young (9 weeks) and old (27 months) male Wistar rats	10 to the minus 4 through 10 to the minus 6 molar	Applied continuously during perifusion	In vitro perifusion	Single experimentNot applicable	Journal of Endocrinological Investigation (PubMed)2003
Melatonin secretion did not change at any concentration at either age, and the rise in melatonin triggered by the beta-adrenergic agonist isoproterenol was also unmodified. The authors, who included Khavinson and Anisimov, concluded that the tetrapeptide does not appear to take part in the control of melatonin secretion by the rat pineal gland in vitro, which argues against a direct action on the gland.
Independent replication of the telomerase result in human cell linesBreast cancer lines 21NT and BT474, plus a normal fibroblast line and normal mammary epithelial cells	0.5-1 mcg/mL	Daily for 4 days in the cancer lines, daily for 3 weeks in the normal lines	Added to culture medium	4 days or 3 weeks depending on cell typeNot applicable	Biogerontology (PubMed Central)2025
A group at Brunel University London found hTERT messenger RNA up in every line, twelve-fold in one cancer line, but telomerase enzyme activity rose only in the normal cells; the cancer lines lengthened telomeres through alternative lengthening of telomeres instead. Biogerontology later published a correction stating that the wrong figures had appeared as Figures 1 to 3, which are all three data figures in the paper, and supplying replacements.
Community-reported4 rows
Ten-day pulsed course with reconstitution math	10 mg per day (100 mg cumulative); 5 mg per day for 20 days given as the same total spread wider	Once daily	Subcutaneous	10 days (or 20 days at the lower dose)No dosing for months 2-6, with the course repeated every 4-6 months, 2-3 times a year	Community resource2026
This calculator page treats the 10-day, 100 mg course as the standard and frames the compound as pulsed rather than run continuously, which it contrasts with how growth hormone secretagogues are cycled. It gives the arithmetic for a 10 mg vial in 1 mL of bacteriostatic water, where a 5 mg dose is 50 units on a U-100 syringe, and states the compound is not FDA approved for anything.
The two named protocols in circulation	10 mg per dose in both	Daily for 10 days in one protocol; on days 1, 5, 9, 13 and 17 in the other	Subcutaneous, in one injection or split between morning and bedtime	10 days (100 mg total) or 17 days (50 mg total)Up to two courses a year, with at least 4 months between them	Community resource2026
This chart names the two schedules the Russian and Ukrainian protocols and attributes both to the International Peptide Society's reading of Khavinson's work. The shorter one doubles the cumulative amount of the longer one, and neither schedule corresponds to any dose given to a person in a published study of the synthetic tetrapeptide.
Course with the source's own evidence caveat	5-10 mg	Once daily, 1-2 hours before bed	Subcutaneous	10-20 day course3-6 months off, with 1-3 courses a year	Community resource2026
This protocol page carries the bluntest caveat of the group on its own figures: no published human study has given the synthetic tetrapeptide by subcutaneous or intramuscular injection at any dose, the 5-10 mg range is 10 to 20 times the only systemic human dose on record, and the Russian clinical work it is usually credited to used epithalamin rather than the peptide. It also lists evening timing on the reasoning that the compound is tied to melatonin.
Route and intensity comparison table	5-10 mg per day subcutaneous; 5 mg per day as the conservative option; 30-50 mg per day total intranasal, split across doses	Once daily by injection; several times daily intranasally; 5 mg every other day for a first course	Subcutaneous or intranasal	10-20 daysTwice a year, often described as spring and autumn; some practitioners run 10-day mini-courses quarterly	Community resource2026
This page tabulates the standard, conservative and intranasal variants side by side and multiplies the intranasal amount severalfold to account for lower absorption. It states that the evidence base is narrow and drawn largely from one research lineage, that the compound is not FDA approved in the United States, and that the quarterly pattern has less published support than the twice-yearly one.

How a course is commonly described

Days 1-10Community-reported
The most-repeated course is 10 mg once daily by subcutaneous injection for ten consecutive days, usually in the evening, for a cumulative 100 mg. Guides describe the compound as pulsed rather than continuous, so the course ends on a fixed day rather than when an effect appears.
Days 11-20 (wider variants)Community-reported
Two alternatives stretch the same course: 5 mg daily for 20 days, which keeps the 100 mg total, and a 17-day schedule of 10 mg on days 1, 5, 9, 13 and 17, which halves it to 50 mg. Nothing published compares the three.
Months 2-6: offCommunity-reported
No dosing between courses. The stated reasoning is that the compound acts at a regulatory level, so a short pulse is treated as sufficient and continuous use as unnecessary, a rationale that rests on the animal work rather than on any human measurement.
Repeat coursesCommunity-reported
One to three courses a year, most often two timed to spring and autumn, with some practitioners substituting 10-day mini-courses every three months. The pages that describe the quarterly pattern note it has less published support than the twice-yearly one.
Clinical comparisonClinical
The only systemic human dosing on record for the synthetic tetrapeptide is 0.5 mg a day as a sublingual spray for 20 days, which measured a urinary melatonin metabolite and clock-gene expression rather than any clinical outcome. The eye study used 5 mcg per eye beside the eyeball for 10 days. No human study has used the subcutaneous route at all.

Nothing validates the 10 mg subcutaneous course. The only systemic human dose published for the synthetic tetrapeptide is 0.5 mg a day under the tongue for 20 days, roughly 20 times lower, and FDA reported finding no study of the subcutaneous route the compound was nominated for.
The human longevity and mortality numbers that circulate under this name were generated with epithalamin, the bovine pineal extract, and with the thymic preparation thymalin, not with the tetrapeptide. PubChem lists Epithalamin and Epithalamine as synonyms of this record, which is one route by which the two get merged in secondary write-ups.
FDA found no pharmacokinetic data in any species and no clinical study of safety in people, flagged aggregation and peptide-related impurities as immunogenicity risks for an injectable, and raised a mechanistic carcinogenicity concern on the grounds that telomerase activation and longer telomeres are associated with higher cancer risk. It judged the mouse tumour studies too limited in dose range, sex and duration to settle that question.

Sources for this section (16)

Overview of Epitalon: Highly Bioactive Pineal Tetrapeptide with Promising PropertiesInternational Journal of Molecular Sciences (PubMed Central)2025Clinical
Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosaNeuroendocrinology Letters (PubMed)2002Clinical
AEDG Peptide Regulation of the Expression of Human Circadian Rhythm Genes upon Accelerated Aging of the Pineal GlandAdvances in Gerontology (Springer)2021Clinical
AEDG peptide regulates human circadian rhythms genes expression during pineal gland accelerated aging (Russian original)Advances in Gerontology (PubMed)2020Clinical
Epitalon-related Bulk Drug Substances: FDA presentation to the Pharmacy Compounding Advisory Committee, July 23-24 2026US Food and Drug Administration2026Clinical
Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR miceBiogerontology (PubMed)2003Preclinical
Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu miceBulletin of Experimental Biology and Medicine (PubMed)2002Preclinical
Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimesBulletin of Experimental Biology and Medicine (PubMed)2007Preclinical
Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old ratsJournal of Endocrinological Investigation (PubMed)2003Preclinical
Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activityBiogerontology (PubMed Central)2025Preclinical
Effect of Peptide AEDG on Telomere Length and Mitotic Index of PHA-Stimulated Human Blood LymphocytesBulletin of Experimental Biology and Medicine (PubMed)2019Preclinical

Plus 5 community resources (dosing guides, forum threads and vendor write-ups), reported above but not linked.

Overview

Epithalon, also written Epitalon, is the synthetic tetrapeptide Ala-Glu-Asp-Gly. Vladimir Khavinson's group at the St Petersburg Institute of Bioregulation and Gerontology assembled it from the amino acid composition of epithalamin, a low molecular weight peptide extract of cattle pineal glands, and reported detecting the same sequence inside a pineal polypeptide complex in 2017. Almost the whole literature comes from that one institute and is in cell culture, fruit flies, mice, rats and two short monkey experiments, where it is described as inducing telomerase, shifting gene expression and restoring evening melatonin in old animals, while a direct test on perifused rat pineal glands found no effect on melatonin at all. Human work amounts to a parabulbar injection study in retinitis pigmentosa and a 20-day sublingual spray study in night-shift workers; the mortality figures quoted for elderly people came from epithalamin, the extract, which PubChem also lists as a synonym of this record. FDA evaluated it for insomnia in 2026, found no pharmacokinetic data and no clinical safety study, and proposed that neither the free base nor the acetate be added to the 503A Bulks List, while one 2026 evidence review reports that the advisory committee voted to recommend adding it anyway by the narrowest margin of the seven peptides considered.

What researchers are exploring

These themes describe recurring questions in published research. They are not claims of effectiveness or recommendations for use.

1
Telomere biology
Cell studies report hTERT/telomerase activity and telomere-length changes.
2
Circadian and pineal research
Early literature examines melatonin rhythms and pineal-associated aging.
3
Gerontology
Small regional studies report aging-related endpoints with limited independent replication.
4
Gene regulation
Laboratory studies explore chromatin and gene-expression effects of short peptides.

What the current evidence can support

Study models remain visible so laboratory and animal findings are not mistaken for established human outcomes.

In vitro
Human-cell telomerase study
A 2003 paper reported telomerase activation and telomere elongation in cultured human somatic cells.
In vitro
Independent 2025 cell replication
A later study reported dose-dependent telomere effects across normal and cancer cell lines.
Review
Clinical longevity claims remain unproven
Cellular telomere findings do not show lifespan extension or clinical benefit in people.

Amounts recorded for Epithalon

These amount records are independent from vial strength, reconstitution volume and measuring device. A recorded source is not the same as study backing, and these values are not recommendations.

1
Recorded referenceSign in for schedule, duration and source context.
1 mg
2
Dose · upper endpointSign in for schedule, duration and source context.
5 mg

Chemistry identifiers

Sequence, synonyms and registry identifiers as recorded in PubChem, the National Library of Medicine's open chemistry database. Formula, mass and CAS number are summarized at the top of the page.

Sequence

Ala-Glu-Asp-Gly

Also listed as

Epitalon, Epithalone, AEDG peptide, Ala-Glu-Asp-Gly, AE-0 peptide, UNII O65P17785G, CHEBI:230091, Epitalon acetate (CAS 307297-40-1, a separate FDA substance record)

InChIKey

HGHOBRRUMWJWCU-FXQIFTODSA-N

Origin / design

Designed from research on pineal peptide extracts

IUPAC name

(4S)-4-[[(2S)-2-aminopropanoyl]amino]-5-[[(2S)-3-carboxy-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid

Limitations and unknowns

Important limitations

Most publications originate from a small interconnected research network.
No large independently replicated randomized human trial establishes anti-aging benefit.
Telomerase activation has context-dependent theoretical risks and is not inherently beneficial.
A calculator preset is a recorded research convention, not a recommendation or evidence of clinical benefit.
Identity, purity, sterility, and stability can vary substantially outside regulated manufacturing.
Route, formulation, and population can make results from one study inapplicable to another use.

Sources

2 curated references, each with its journal, year and study model, plus 5 community resources reported but not linked.

Epithalon peptide induces telomerase activity and telomere elongation in human somatic cellsBulletin of Experimental Biology and Medicine2003In vitro
Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activityBiogerontology2025In vitro

How sourced amounts are organized

Patterns described in source material

Storage, handling and interpretation

How a course is commonly described

What researchers are exploring

Telomere biology

Circadian and pineal research

Gerontology

Gene regulation

Human-cell telomerase study

Independent 2025 cell replication

Clinical longevity claims remain unproven

Sequence

Also listed as

InChIKey

Origin / design

Important limitations