Epitalon · Epithalone · AEDG · CAS 307297-39-8 · MW 390.35 g/mol · Linear Tetrapeptide
A synthetic tetrapeptide (Ala-Glu-Asp-Gly) derived from the amino acid composition of Epithalamin, a naturally occurring polypeptide complex isolated from bovine pineal gland tissue. Epithalon has been studied for over 25 years across in-vitro, in-vivo, and limited clinical contexts for its roles in telomere biology, neuroendocrine regulation, circadian rhythm modulation, and geroprotective activity.
Pineal Tetrapeptide Telomerase Activator ≥99.0% HPLC Purity Lyophilized 10 mg / vial CoA Included Cold Shipped
Purity
≥99.0%
Molecular Weight
390.35 g/mol
Sequence
Ala-Glu-Asp-Gly
Testing Lab
Freedom Diagnostics
01 Mechanism of Action
Epithalon is a bioregulatory tetrapeptide whose precise mechanism of action remains an active area of investigation. Unlike receptor-ligand peptides with well-characterised binding targets, Epithalon appears to exert its biological effects through several converging pathways, the most studied of which involves the telomere maintenance machinery of dividing cells.
The compound has been detected in physiological pineal gland extract (confirmed 2017), suggesting it is an endogenous signalling molecule rather than a purely synthetic construct. It is believed to reach nuclear targets by penetrating cell membranes — a property consistent with its small size and hydrophilic character — and has been shown to interact with histone H1 proteins, which may mediate its reported epigenetic and chromatin-remodelling effects.
Telomerase Activation
Epithalon upregulates hTERT (human telomerase reverse transcriptase) expression in somatic cell lines, increasing telomerase enzyme activity and enabling extension of telomeric repeat sequences. This counteracts the progressive telomere shortening associated with each cell division cycle and may delay onset of replicative senescence in certain cell types.
Circadian / Melatonin Regulation
Epithalon has been associated with restoration of melatonin secretion rhythms in aged primate models where pineal output has declined. It is hypothesised to act on the pineal gland’s regulatory feedback circuitry, normalising the amplitude and phasing of melatonin release.
Epigenetic Modulation
Chromatin remodelling events have been observed in cultured human leukocytes following Epithalon exposure. Binding to linker histone H1 subtypes (H1.3, H1.6) may alter nucleosome spacing and gene accessibility, potentially affecting transcription factor access to promoter regions involved in cell cycle regulation.
Antioxidant & Immune Signalling
Preclinical studies report modulation of interleukin-2 mRNA levels and mitogenic activity in murine thymocytes, as well as enhanced activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Antioxidant activity has been observed in rodent tissue.
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Mechanistic Note: While telomerase activation is the most widely cited mechanism, recent research (2025) demonstrates that Epithalon may operate through differential pathways depending on cell type — activating telomerase in normal somatic cells while potentially inducing ALT (Alternative Lengthening of Telomeres) recombination mechanisms in cancer cell lines via H1 histone binding and H19 lncRNA upregulation.
02 Research Applications & Evidence Base
Epithalon’s research history spans more than 25 years and encompasses in-vitro cell studies, rodent and primate longevity models, and a limited number of human clinical investigations.
Telomere Biology & Cellular Senescence
The most extensively documented in-vitro activity of Epithalon is its effect on telomere length in human cell lines. Treatment of human fetal fibroblasts demonstrated measurable telomere elongation via TRAP assay, and treated cells were observed to exceed their normal Hayflick limit. More recent work (2025, PMC12411320) confirmed telomere length increases across multiple breast epithelial and cancer cell lines.
Longevity & Geroprotection (Animal Models)
Multiple rodent studies — primarily in female SHR mice and Wistar rats — have reported extended median and maximum lifespans in Epithalon-treated cohorts versus controls. A 2003 study in Biogerontology reported suppressed spontaneous tumour incidence alongside lifespan extension.
Model / System
Reported Effect
Evidence Level
Key Limitation
Human fibroblasts (in vitro)
Telomere elongation; Hayflick limit extension
In vitro, replicated 2025
Cell line variability
Female SHR mice
Extended lifespan; reduced tumour incidence
In vivo, single lab
No independent replication
Aged primates
Restored melatonin amplitude
In vivo, abstract only
Full paper unavailable
Elderly humans (epithalamin)
Improved cardiovascular / immune markers
Clinical, n=266 / n=70
Parent compound; not replicated
Human leukocytes (in vitro)
Chromatin remodelling; epigenetic changes
In vitro
Mechanism not fully elucidated
Evidence Strength by Research Area
Telomerase activation
Strong in vitro
Telomere elongation
Strong in vitro
Melatonin modulation
Mixed evidence
Lifespan extension
Animal, single lab
Human clinical effects
Limited, indirect
Anti-tumour activity
Preclinical only
03 Observed Research Effects
Telomere length extension (in vitro)
Enhanced telomerase (hTERT) expression
Melatonin rhythm normalisation
Improved sleep architecture markers
Reduced oxidative stress markers
IL-2 mRNA modulation
Enhanced AChE / BuChE activity
Improved cardiometabolic indices (elderly)
Reduced spontaneous tumour incidence (rodents)
Retinal preservation (dystrophy model)
Safety Profile & Research Caveats
Telomerase activation in oncological contexts — Telomerase upregulation is a double-edged mechanism. While beneficial for healthy cell longevity, elevated telomerase activity is also a hallmark of cancer cell immortalisation. The 2025 PMC study suggests Epithalon may behave differently in cancer vs. normal cells, but this differential activity has not been systematically characterised.
Independence of evidence base — The substantial majority of published Epithalon research originates from a single group (Khavinson et al., St. Petersburg Institute of Bioregulation and Gerontology). Independent replication of key in-vivo findings has not been published.
Parent vs. synthetic compound discrepancy — Some effects reliably reported for Epithalamin (the crude pineal extract) have shown inconsistent results with the isolated synthetic tetrapeptide. Purity certification is therefore especially important.
Long-term safety data gaps — No large-scale, long-duration randomised controlled trial of synthetic Epithalon in humans has been published.
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Research Use Only. The effect profile above is derived from peer-reviewed preclinical and limited clinical literature. Peplix supplies Epithalon exclusively for in-vitro laboratory and preclinical research.
04 Chemical & Physical Profile
Full NameEpithalon (Epitalon / AEDG)
CAS Number307297-39-8
Molecular FormulaC₁₄H₂₂N₄O₉
Molecular Weight390.35 g/mol
Structure TypeLinear tetrapeptide, all L-amino acids
SequenceH-Ala-Glu-Asp-Gly-OH
OriginSynthetic; derived from Epithalamin (bovine pineal extract)
Endogenous StatusDetected in human pineal tissue (Khavinson et al., 2017)
SolubilityFreely soluble in water; stable at neutral pH
Storage−20°C (lyophilized); 2–8°C reconstituted; protect from light
Peplix Purity≥99.0% by HPLC
Testing LabFreedom Diagnostics
Lot Number2603
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Purity Note: Historical discrepancies between Epithalon research results have been partially attributed to impurities in early synthetic preparations. Peplix sources Epithalon at ≥99.0% HPLC purity with full mass spectrometry verification. Contact support@peplix.bio to request CoA documentation.
05 Reconstitution Reference
BAC Water Added
Concentration
Vol per 100 µg
Vol per 1 mg
1.0 mL
10,000 µg/mL
10 µL
100 µL
2.0 mL
5,000 µg/mL
20 µL
200 µL
5.0 mL
2,000 µg/mL
50 µL
500 µL
10.0 mL
1,000 µg/mL
100 µL
1.00 mL
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Protocol Note: Epithalon dissolves readily — inject bacteriostatic water slowly along the vial wall and swirl gently. Do not vortex. Reconstituted solution stable at 2–8°C for up to 4 weeks. Use the Reconstitution Calculator for precise volumes.
06 Research Literature
Araj H et al. Epitalon increases telomere length through telomerase upregulation or ALT activity. PMC12411320. 2025.
Khavinson VK et al. Overview of Epitalon — Highly Bioactive Pineal Tetrapeptide. PMC11943447. 2025.
Anisimov VN et al. Effect of Epitalon on biomarkers of aging and life span in female SHR mice. Biogerontology. 2003;4:193–202.
Khavinson VK, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuroendocrinol Lett. 2003;24:233–240.
Khavinson VK et al. Pineal-regulating tetrapeptide improves eye retina condition in retinitis pigmentosa. Neuroendocrinol Lett. 2002;23(4):365–368.