Epitalon
Animal-onlyEpithalon · Epithalone · AEDG peptide · Ala-Glu-Asp-Gly
Limited evidence: the strongest curated study is Animal-only; no human-trial data found as of 2026-06-04.
Chemical & identity
- Sequence
- AEDG
- Length
- 4 residues
- Molecular formula
- C14H22N4O9
- Molecular weight
- 390.35 g/mol · PubChem
- PubChem CID
- 219042 · PubChem
- SMILES
- C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N
- InChIKey
- HGHOBRRUMWJWCU-FXQIFTODSA-N
- Category
- Longevity
Chemical/structural fields are auto-pulled and source-linked.
Mechanism (curated)
Synthetic pineal tetrapeptide (AEDG); proposed to upregulate telomerase / lengthen telomeres and to modulate pineal melatonin signaling and gene expression. These mechanisms are largely preclinical and not established in humans.
Pharmacology & handling
- Half-life
- Short — small tetrapeptide rapidly degraded by peptidases.
Research
Khavinson V et al. · Molecules (Basel, Switzerland) · 2020 · In-vitro study
This in-vitro study investigated how AEDG peptide (epitalon) affects neurogenic gene expression and protein synthesis in human gingival mesenchymal stem cells (hGMSCs). The peptide increased synthesis and mRNA expression of neurogenic differentiation markers (Nestin, GAP43, β Tubulin III, Doublecortin) by 1.6–1.8 times. Molecular modelling suggested the peptide preferentially binds to H1/3 and H1/6 histones at specific DNA-interacting sites, which may explain how it enhances neuronal differentiation gene transcription. The authors propose this represents an epigenetic mechanism of action.
Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa.
AnecdotalKhavinson V et al. · Neuro endocrinology letters · 2002 · Other
This study examined the tetrapeptide epitalon (Ala-Glu-Asp-Gly) in retinitis pigmentosa, a congenital retinal degeneration. In Campbell rats, epitalon increased bioelectric and functional retinal activity while preserving retinal morphology. In patients with degenerative retinal lesions, epitalon therapy produced positive clinical effects in 90% of cases. The authors propose that epitalon acts through transcription mechanisms shared by the pineal gland and retina.
Ivko OM et al. · Advances in gerontology = Uspekhi gerontologii · 2020 · Other
This study examines the AEDG peptide (Ala-Glu-Asp-Gly), a tetrapeptide proposed as a geroprotector for pineal gland aging. The abstract reports that AEDG peptide increases urinary 6-sulfatoxymelatonin excretion by 1.7-fold in middle-aged people and normalizes expression of circadian Clock and Csnk1e genes while modulating Cry2 gene expression in peripheral blood lymphocytes of individuals with reduced melatonin-producing function. The study claims the peptide's geroprotective effect operates through restoration of pineal melatonin synthesis via regulation of circadian gene expression. No explicit study design, control group, or sample size is detailed in the abstract.
Araj SK et al. · International journal of molecular sciences · 2025 · Narrative review
Epitalon is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) derived from bovine pineal gland extract that has been studied over 25 years using in vitro, in vivo, and in silico methods. The abstract reports that epitalon demonstrates geroprotective and neuroendocrine effects attributed to antioxidant, neuroprotective, and antimutagenic properties. Documented effects include influence on melatonin synthesis, altered interleukin-2 mRNA levels, modulation of thymocyte mitogenic activity, and enhanced activity of enzymes including AChE, BuChE, and telomerase, though the abstract notes uncertainty about whether these represent the sole mechanisms of action. The abstract indicates that while biological and pharmacodynamic research is extensive, physicochemical and structural investigations of epitalon remain limited. This is a narrative review article summarizing the state of knowledge on epitalon.
Khavinson VK et al. · Mechanisms of ageing and development · 2000 · Animal study
This study examined the geroprotector activity of epitalon, a synthetic tetrapeptide (Ala-Glu-Asp-Gly), in Drosophila melanogaster (Canton-S wild strain). Epitalon was added to culture medium during the developmental stage (egg to larva) and significantly increased lifespan of adult flies by 11–16% at very low concentrations (0.001 × 10⁻⁶ to 5 × 10⁻⁶ wt.% for males; 0.01 × 10⁻⁶ to 0.1 × 10⁻⁶ wt.% for females). The lifespan increase was independent of dose, and the effective concentrations were substantially lower than those required for melatonin. The authors discuss potential antioxidant and regulatory mechanisms underlying epitalon's effects.
Gatta M et al. · Stem cell reviews and reports · 2025 · In-vitro study
This in-vitro study investigated whether the tetrapeptide epitalon (AEDG) could improve delayed wound healing in diabetic retinopathy using a high-glucose-injured human retinal pigment epithelial cell line (ARPE-19). High glucose exposure delayed wound healing, increased reactive oxygen species levels, and decreased antioxidant gene expression. Epitalon restored impaired wound healing by inhibiting hyperglycemia-induced epithelial-mesenchymal transition and fibrosis-related gene upregulation. The authors propose epitalon as a potential therapeutic agent for diabetic retinopathy and suggest that further mechanistic investigation and development of ophthalmic formulations are needed.
Vinogradova IA et al. · Bulletin of experimental biology and medicine · 2007 · Animal study
This animal study examined the effects of the Ala-Glu-Asp-Gly peptide (Epithalon) on lifespan and spontaneous tumor development in female rats under three illumination conditions: standard, natural (North-Western Russia), and constant light. Epithalon at 0.1 microg daily, five times weekly from age 4 months, did not affect lifespan in rats under standard lighting but prolonged maximum lifespan by 95 days and 24 days in rats exposed to natural and constant illumination, respectively. The peptide significantly inhibited spontaneous tumor development only in rats exposed to natural illumination, with minimal or no effect under standard and constant lighting conditions.
Anisimov VN et al. · International journal of cancer · 2002 · Animal study
This animal study tested epitalon (Ala-Glu-Asp-Gly), a tetrapeptide, and vilon (Lys-Glu), a dipeptide, in female FVB/N HER-2/neu transgenic mice by subcutaneous injection (1 μg/mouse for 5 consecutive days monthly starting at 2 months of age). Epitalon treatment reduced cumulative tumor number, maximum tumor size, and the number of mice bearing multiple tumors, while lung metastasis size (but not number) was also reduced. Epitalon reduced HER-2/neu mRNA expression 3.7-fold in mammary tumors compared to controls, and the authors suggest this downregulation may explain the antitumor effect. Vilon showed opposite effects, increasing tumor incidence and cumulative number compared to saline controls.
Anisimov VN et al. · Biogerontology · 2003 · Animal study
A study in female outbred Swiss-derived SHR mice (n=54 per group) administered Epitalon (1.0 µg/mouse, ~30–40 µg/kg) or saline monthly from 3 months of age until death. Epitalon did not affect food consumption, body weight, or mean lifespan, but slowed age-related decline in estrous function and reduced chromosome aberrations in bone marrow cells by 17.1%. The treatment increased maximum lifespan by 12.3% and the lifespan of the last 10% of survivors by 13.3%, and inhibited leukemia development 6-fold while having no effect on total tumor incidence. The authors conclude Epitalon has geroprotector activity and is safe for long-term use in mice.
Anisimov VN et al. · Cancer letters · 2002 · Animal study
This study examined the effect of the synthetic peptide Epitalon (Ala-Glu-Asp-Gly) on colon carcinogenesis in rats. Eighty male rats were exposed to the carcinogen 1,2-dimethylhydrazine and treated with either saline (control), Epitalon during carcinogen exposure, Epitalon after carcinogen exposure, or saline alone. Epitalon treatment during carcinogen exposure (group 2) and during the DMH exposure period (group 4) resulted in significantly reduced tumor numbers compared to control, with group 2 showing smaller tumors and decreased incidence and multiplicity in ascending and descending colon. The study also found a trend toward decreased rectal tumors and inhibited development of tumors in jejunum and ileum with Epitalon treatment.
Effects of intranasal administration of epitalon on neuron activity in the rat neocortex.
Animal-onlySibarov DA et al. · Neuroscience and behavioral physiology · 2007 · Animal study
This study examined the effects of intranasal epitalon (a synthetic tetrapeptide Ala-Glu-Asp-Gly) on spontaneous neuron activity in the rat neocortex. Male Wistar rats anesthetized with urethane received intranasal epitalon (30 ng per animal) while extracellular cortical neuron activity was recorded. Epitalon induced significant activation of neuron discharge frequency, with increases of 2–2.5 fold occurring several minutes after administration. The effect was sometimes multiphasic, with peaks at 5–7, 11–12, and 17–18 minutes, involving both increased firing of already-active neurons and recruitment of previously silent neurons. The first peak of increased activity was attributed to direct action of epitalon on cortical cells.
Anisimov VN et al. · Bulletin of experimental biology and medicine · 2002 · Animal study
This animal study investigated epithalon (Ala-Glu-Asp-Gly), a synthetic peptide, in female transgenic FVB/N mice carrying the HER-2/neu breast cancer gene. Mice received epithalon 1 mg subcutaneously five times weekly from 2 months of age until death. Epithalon extended average and maximum lifespans by 13.5% and 13.9%, increased the proportion of tumor-free mice, reduced breast adenocarcinoma incidence, lung metastases (1.6-fold reduction), and multiple tumors (2-fold reduction), while extending survival of tumor-bearing mice by 1.4-fold. The authors concluded epithalon has geroprotective activity and inhibits breast carcinogenesis in this transgenic model, possibly through suppression of HER-2/neu expression.
Al-Dulaimi S et al. · Biogerontology · 2025 · In-vitro study
Epitalon, a naturally occurring tetrapeptide, was studied in human breast cancer cell lines (21NT, BT474) and normal epithelial and fibroblast cells. Treatment with epitalon resulted in dose-dependent telomere length extension in normal cells through upregulation of hTERT mRNA expression and telomerase enzyme activity, as measured by qPCR and immunofluorescence analysis. In cancer cells, significant telomere length extension also occurred through ALT (Alternative Lengthening of Telomeres) activation, with only minor ALT activity in normal cells. The study suggests epitalon can extend telomere length in normal mammalian cells via hTERT upregulation and telomerase activation.
Summaries are our own; we link to originals (PubMed / DOI) and never rehost full text.
Regulatory status
- FDA approved
- No
- WADA prohibited
- No
- Compounding status
- Not an approved drug; marketed as an experimental 'peptide bioregulator'.
- Notes
- Not FDA-approved and not an approved drug; sold as an experimental peptide. Human clinical evidence is very limited. As of 2026-06-04, not listed on the WADA prohibited list.
Legal/regulatory status varies by jurisdiction and changes over time — accurate as of last review (2026-06-04).
Data sources: Curated IDs (PubChem/UniProt/ChEMBL) + Europe PMC + ClinicalTrials.gov (2026-06-04).
Last reviewed 2026-06-04