Epithalon 10mg

Product status information

Chemical reagent intended exclusively for laboratory tests (Research Use Only). It is not a medicinal product, dietary supplement or food. It is not intended for use on humans or animals. Sales only to registered research units and laboratories.

In the mid-1980s in Leningrad, Vladimir Chawinson’s team isolated a peptide extract – epithalamin – from the pineal gland of calves and observed an extension of lifespan and normalization of the circadian rhythm in rodent models. The problem was technical: the extract is a mixture of uncertain composition, difficult to standardize and repeat between batches.

The answer was the synthesis of a short peptide mapping the core activity – Epithalon, tetrapeptide Ala-Glu-Asp-Gly (AEDG). Four amino acids, one repeating sequence, controllable purity. Three decades later, Epithalon remains one of the most frequently cited compounds in the literature on the biology of aging — largely due to observations in vitro, in which the peptide induced telomerase activity in human somatic cells (Chawinson et al. 2003).

However, the molecule has not completed any clinical phase III, is not registered as a drug and remains a research tool. Most of the data comes from the Russian school of peptide bioregulation (Khawinson, Anisimov) and requires independent replication. This reagent from the line Endogenic is delivered as single vial of lyophilisate, 10 mg Epithalon — format for research protocols with a single series or for starting work with compounds, without involving a larger pool of material.

A separate set format is dedicated to researchers planning a longer time horizon with repeatable series (Epithalon 10mg 4+1 free — five vials from one batch pool). Reconstitution with bacteriostatic water before experimental work.

The pineal gland (epiphysis) is a small gland in the midbrain that synthesizes melatonin and participates in the regulation of the circadian rhythm and the neuroendocrine axis. In models of aging, a gradual decline in its secretory activity is observed – a phenomenon that the Russian school of molecular gerontology has put at the center of the hypothesis of an “aging clock” controlled by the pineal gland.

From this hypothesis arose the concept peptide bioregulation — research school of the St. Petersburg Institute of Bioregulation and Gerontology (Vladimir Khavinson, Vladimir Anisimov). Premise: short research peptides of a regulatory nature, reflecting fragments of endogenous tissue extracts, modulate gene expression in a tissue-specific manner. Epithalamin (pineal gland extract) was the prototype; Epithalon (AEDG) – its synthesized, standardized analogue with a defined sequence of four amino acids.

The world of pharmacology is watching Epithalon for three reasons. First, as a research tool telomerase regulation in somatic cells – an area where there are few small-molecule modulators of hTERT expression. Secondly, as a model compound for chronobiology and the pineal-hypothalamic axis in rodent models. Third, as a representative of the class of “peptide geroprotectors” – short peptides studied for their effects on aging markers and lifespan in animal models.

In all three directions, the research material must be chemically repeatable – and here HPLC purity and MS identity confirmation are important, because short peptides are easily contaminated with products of incomplete synthesis.

Chemically, Epithalon is a linear tetrapeptide with the sequence Ala-Glu-Asp-Gly.

• Common name: Epithalon, Epitalon, Epithalone
• Full sequence name: H-Ala-Glu-Asp-Gly-OH (Alanyl-glutamyl-asparaginyl-glycine)
• Sequence abbreviation: AEDG (amino acid single letter code)
• Synonyms: Epitalon, Epithalone, a synthetic analogue of epithalamine
• Class: synthetic regulatory tetrapeptide; epithalamine analogue (pineal peptide)
• Product line: Endogenic
• CAS number: 307297-39-8
• Molecular formula: C₁₄H₂₂N₄O₉
• Molar mass: 390.35 g/mol
• Delivered form: lyophilisate in a vial, 10 mg of active substance, single vial; reconstitution with bacteriostatic water; pharmaceutical grade ≥98% HPLC

Table of physicochemical characteristics

Origin: Epithalon was developed by Vladimir Chawinson in St. Petersburg Institute of Bioregulation and Gerontology as a synthetic analogue of epithalamine – a peptide extract of the pineal gland studied since the 1970s–1980s. 20th century. Goal of synthesis: replace non-standardized tissue extract with a defined, repeating sequence of four amino acids. The main body of research was conducted by Russian teams (Chawinson, Anisimow, Korkuszko) in the field of peptide bioregulation – with an emphasis on telomerase, circadian rhythm and aging markers in rodent models and cell cultures.

The molecule has not been registered as a drug in any jurisdiction and has not passed clinical phase III in humans.

Epithalon is described in the literature by several parallel regulatory mechanisms. There is no clearly identified primary receptor – the Chawinson school model assumes direct modulation of gene expression (the “peptide bioregulation” mechanism), and not classic signaling through a membrane receptor.

Telomerase activation in somatic cells (in vitro)

Most frequently cited observation. Telomerase is an enzyme that lengthens telomeres – the end sections of chromosomes that shorten with each somatic cell division, determining the so-called Hayflick limit (finite number of divisions). In human fibroblast cultures, Epithalon induced the expression of the telomerase catalytic subunit (hTERT), which was accompanied by elongation of telomeres and an increase in the number of cell divisions – in the work of Chawinson et al. (2003), the Hayflick limit was described in vitro.

In experimental practice, this means: cells in culture were dividing longer than their “replication clock” would indicate. This is an observation at the cell culture level – not evidence of an extension of the organism’s lifespan.

Circadian modulation and melatonin synthesis

As a pineal peptide analogue, Epithalon in rodent models influenced melatonin synthesis and normalization of the circadian rhythm, especially in older animals with weakened pineal gland function. The mechanism is associated with the pineal-hypothalamic axis. In practice: in aging models, a shift in the melatonin secretion profile towards the nocturnal amplitude characteristic of younger animals was observed.

Antioxidant and geroprotective effects (rodent models)

In mouse and rat models (including the SHR mouse), Anisimow’s work described the reduction of oxidative stress markers and the impact on survival parameters in long-term exposure protocols. Some studies reported an extension of the median lifespan and modulation of the incidence of spontaneous cancers in animal cohorts – these observations come mainly from one research stream and require independent replication.

Regulation of gene expression (epigenetic mechanism)

The Chawinson school model assumes that short regulatory peptides have activity at the level of gene expression – direct interaction with specific DNA sequences and modulation of the expression of regulatory genes were proposed. This is the core concept of “peptide bioregulation”. The molecular details of this interaction (affinity, sequence specificity) remain a matter of debate and have not been fully characterized outside the original mainstream.

Neuroendocrine modulation

In aging models, Epithalon has been described as a compound that normalizes the function of the hypothalamic-pituitary axis – restoring a neuroendocrine signaling profile similar to younger animals in rodent models. The mechanism is probably indirect, through the pineal-hypothalamic axis.

IMPORTANT DISTINCTION

“Telomerase activation” in the context of this description refers only to the observation of the induction of hTERT expression and telomere elongation in in vitro human cell cultures (Chawinson et al. 2003). This is not the same as “extending human lifespan”, “reversing aging”, or “lengthening telomeres in a person using the reagent”. Telomerase activity in isolated cell culture and the effect on the aging process of the entire organism are two separate levels of observation – the first does not prove the second.

There are no human clinical trials (RCTs) assessing the effects of Epithalon on in vivo telomere length, aging biomarkers, or survival. Communications such as “longevity peptide”, “cellular rejuvenation” or “telomere lengthening” are contrary to the Research Use Only framework and go beyond what has been demonstrated in the literature.

Epithalon is used in research work in several areas. In models in vitro (human fibroblasts, somatic cell lines, cultures with senescence markers) its influence on hTERT expression, telomere length and the number of cell divisions is examined. In models in vivo (SHR mouse, rat) survival parameters, oxidative stress markers, melatonin secretion profile and the function of the neuroendocrine axis are analyzed in long-term exposure protocols.

A single 10 mg vial works well as a starting material for such a single batch – when researchers are just bringing the compound into the workshop or planning a shorter protocol without a stockpile between batches. Specific research directions include:

• Telomerase regulation and replicative senescence — measurement of hTERT expression (qPCR, Western blot), telomere length (TRF, telomere qPCR), number of cell passages until senescence; Epithalon as a tool to study pharmacological modulation of the Hayflick limit
• Chronobiology and the pineal-hypothalamic axis — melatonin secretion profile, expression of circadian clock genes (Bmal1, Per, Cry), models of rhythm desynchronization in aging
• Geroprotection in rodent models — survival parameters, oxidative stress markers, incidence of cancer in long-term cohorts (Anisimov’s line of research)
• Profile “peptide geroprotectors” — comparison of Epithalon with other short regulatory peptides of the bioregulation school in terms of impact on aging markers
• Models of regulatory gene expression — research on the proposed epigenetic mechanism of action of short peptides

Epithalon (AEDG, Ala-Glu-Asp-Gly) is a synthetic tetrapeptide developed by Vladimir Chawinson as a standardized analogue of epithalamine – pineal gland extract. Described in the literature mainly due to the induction of telomerase activity (hTERT expression) and telomere lengthening in human somatic cells in vitro (Chawinson et al. 2003), as well as modulation of circadian rhythm and aging markers in rodent models (Anisimov’s line of research).

The mechanism is associated with direct regulation of gene expression (“peptide bioregulation”) and the pineal-hypothalamic axis. Most of the data comes from the Russian school of bioregulation and requires independent replication; no phase III clinical trials in humans. Form: single vial of 10 mg lyophilisate from the Endogenic line, reconstitution with bacteriostatic water, HPLC purity ≥98%, COA for each batch.

For researchers with a longer horizon of repeatable batches, the kit format is dedicated – five vials from one pool of batches. Regulatory Status – Research Use Only; lack of registration as a medicine; WADA status: not listed. A complementary anti-aging reagent to the body of research on skin and tissue regeneration is copper tripeptide GHK-Cu 20mg; ready-made is available in protocols combining both research directions Epithalon GHK-Cu anti-aging stack.

1. Khavinson VK, Bondarev IE, Butyugov AA (2003). Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. PubMed
2. Khavinson VK, Morozov VG (2003). Peptides of pineal gland and thymus prolong human life. PubMed
3. Anisimov VN, Khavinson VK, Popovich IG, et al. (2003). Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. PubMed
4. Korkushko OV, Khavinson VK, Shatilo VB, Antonyuk-Shcheglova IA (2006). Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging. PubMed
5. Ashapkin V, Khavinson V, Shilovsky G, Linkova N, Vanyushin B (2020). Gene expression in human mesenchymal stem cell aging cultures: modulation by short peptides. PubMed