# Epitalon (Epithalon): The Khavinson Pineal Tetrapeptide AEDG — A Literature Digest

> Epitalon is the synthetic AEDG tetrapeptide designed by Vladimir Khavinson's St. Petersburg group from the bovine pineal extract Epithalamin. A textile-layered editorial digest of the telomerase, melatonin, and rodent-lifespan record.

A sober editorial digest of twenty-five years of in vitro telomerase work, rodent geroprotection studies, and small Russian human cohorts — with every quantitative claim cited and every literature limit named.

## What Epitalon is, in one paragraph

Epitalon is a synthetic tetrapeptide with the sequence Ala-Glu-Asp-Gly — the AEDG peptide — designed in the late 1980s and 1990s by Vladimir Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology [1]. The molecule was reverse-engineered from the amino-acid profile of Epithalamin, a crude polypeptide extract of the bovine pineal gland that the Khavinson program had been studying for two decades [1][14]. Its molecular formula is `C14H22N4O9`, its molar mass 390.35 g/mol, and the TFA salt commonly used in research carries the CAS registry number 307297-39-8 [15]. The compound is also catalogued under the spellings [Epithalon (with an h)](/epithalon) and Epithalone — transliterations from the Russian — and a tight definitional page on [what is Epitalon](/what-is-epitalon) covers the same ground for newcomers.

## What the published record has actually measured

Across twenty-five years of work, the Epitalon literature has accumulated three reproducible signals. First, in cultured human cells, AEDG induces expression of the telomerase catalytic subunit hTERT and elongates telomeres — first shown by Khavinson, Bondarev and Butyugov in fetal fibroblasts in 2003 [1] and independently replicated in normal human fibroblasts and epithelial cells by Al-dulaimi and colleagues in *Biogerontology* in 2025 [2]. Second, in rodent geroprotection models, monthly subcutaneous courses at microgram-per-mouse doses have reduced spontaneous tumor frequency in HER-2/neu mice [4], suppressed dimethylhydrazine-induced colon adenocarcinomas in rats [8], and slowed reproductive ageing in Swiss-derived SHR mice without increasing mean lifespan [6]. Third, in elderly human subjects with reduced pineal output, intramuscular courses of the parent extract Epithalamin restored night-time melatonin secretion toward younger-adult patterns [11][12]. The fine print matters: most of this work originates from a single program.

## Ala-Glu-Asp-Gly (AEDG): The Tetrapeptide Sequence

AEDG is the single-letter shorthand for the amino-acid sequence of Epitalon: Alanine–Glutamate–Aspartate–Glycine. Researchers and chemists use 'AEDG peptide' and 'Epitalon' interchangeably in the literature, and the [AEDG peptide sequence](/#aedg) is the structural identifier referenced in most modern Western-indexed papers. The molecule is short and linear, without disulfide bridges or post-translational modifications — four amino acids joined by three peptide bonds, with a free amine at the N-terminus and a free carboxylate at the C-terminus. The 2020 *Molecules* paper by Khavinson and colleagues proposed a histone-binding mechanism for AEDG, modelling preferential interactions with histones H1/3 and H1/6 at their DNA-interactive sites [3]. The 2025 Araj review in the *International Journal of Molecular Sciences* consolidates the structural literature and explicitly notes that formal physicochemical characterisation of the intact tetrapeptide remains an open research gap [15].

## Chemical identity

The tetrapeptide is fully described by sequence H-Ala-Glu-Asp-Gly-OH, molecular formula `C14H22N4O9`, molar mass 390.35 g/mol, and CAS registry 307297-39-8 for the TFA salt commonly used in research [15]. The IUPAC name is (4S)-4-[[(2S)-2-aminopropanoyl]amino]-5-[[(2S)-3-carboxy-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid. As a short, unmodified linear peptide, oral bioavailability of the intact molecule is expected to be poor — and most published work uses parenteral routes (subcutaneous, intramuscular, parabulbar) or in vitro delivery [15].

## What is Epitalon?

Epitalon is the synthetic tetrapeptide Ala-Glu-Asp-Gly (AEDG), developed by Vladimir Khavinson's group in St. Petersburg from the amino-acid composition of the bovine pineal extract Epithalamin [1]. It is studied in the peer-reviewed literature as a putative telomerase activator, a modulator of pineal melatonin rhythm, and a candidate geroprotector in rodent models [2][6][11][15]. It is not an FDA-approved drug for any human indication.

## Research uses

Epitalon is studied as a research tool for telomerase activation in human somatic cell lines [1][2], pineal melatonin regulation in aged subjects [11][12], antitumor effects in rodent models [4][7][8], and as a probe for cellular-aging biomarkers including hTERT expression, telomere length, and oxidative-stress indices [15]. It is not studied — in the peer-reviewed literature — as a cosmetic or appearance-modifying compound; reports of that kind circulate in consumer media but are not anchored to peer-reviewed clinical trial endpoints [15].

## How to read this site

The dossier is organised by what the studies measured. The [Epitalon mechanism of action](/research#mechanism) page walks through the telomerase-induction and histone-binding evidence. The [dosing in published studies](/dosage) page catalogues the routes and doses reported across rodent and human work, with no clinical recommendation attached. The [frequently asked questions](/faq) page collects the questions most often asked about the compound — including [reported side effects](/faq#side-effects), regulatory status, and the realistic limits of what the literature supports. The [Khavinson peptide program](/research#khavinson) section frames the historical context: this is a Russian peptide-bioregulator program with a long internal record and a thin external replication base, and reading the literature without that context produces misleading certainty in either direction.

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A textile-layered editorial digest of the Khavinson pineal tetrapeptide literature — Epitalon and Epithalon read as one molecule, two spellings, and twenty-five years of mostly-Russian record, with the Western trial gap named.
