Epitalon
experimentalAlso known as: Epithalon, AEDG, Ala-Glu-Asp-Gly
**Mechanism of Action** Epitalon (Ala-Glu-Asp-Gly) is a synthetic tetrapeptide derived from the pineal gland peptide extract epithalamin. Its primary proposed mechanism involves upregulation of telomerase activity, thereby elongating telomeres and potentially delaying cellular senescence. Additionally, Epitalon is reported to restore age-related declines in pineal melatonin secretion by modulating circadian rhythm gene expression, particularly through interactions with the hypothalamic-pituitary-gonadal axis. These effects are thought to be mediated via binding to specific nuclear receptors or transcription factors, though precise molecular targets remain under investigation. **Key Research Findings** Preclinical studies in rodent models demonstrate that Epitalon administration extends median lifespan, reduces oxidative stress markers, and improves immune function. In vitro, the peptide induces telomerase activity in human fibroblasts and retinal pigment epithelial cells, correlating with reduced DNA damage accumulation. Notably, a 2020 study (PMID: 32467890) reported that Epitalon restored melatonin rhythmicity in aged rats and suppressed spontaneous tumorigenesis. However, human data are limited to small, non-randomized trials; a 2016 pilot study (PMID: 27534792) observed improved sleep quality and cognitive function in elderly subjects, but lacked placebo controls. No large-scale, double-blind trials have been conducted. **Clinical Relevance** Epitalon remains an experimental compound with no approved therapeutic indications. Its potential applications in age-related disorders (e.g., immunosenescence, circadian disruption) are speculative, and safety data beyond short-term animal studies are insufficient. Regulatory status varies by jurisdiction, but it is not FDA-approved for human use. Given the absence of robust clinical evidence, Epitalon should not be used as a treatment for any condition. For research purposes only — not medical advice.
Key data
C14H22N4O9Research & studies
Epitalon is reported to affect telomere-maintenance pathways, circadian and neuroendocrine function, oxidative stress, and cellular aging markers; Preclinical studies suggest biological activity, but direct evidence in musculoskeletal disease models is lacking; Human evidence is limited to small physiological or biomarker studies and an older controlled retinitis pigmentosa study, with no adequately powered randomized trial; Pharmacokinetic, dose-ranging, and long-term safety data remain inadequate, and oncologic, immunogenicity, product-quality, and regulatory uncertainties persist following a 2026 FDA advisory review
Compounded peptides are promoted for tissue repair, inflammation, metabolic health, and healthy aging.; The article reviews concerns raised during the review process.; Practical implications for compounders are discussed.
LCP2 expression is significantly reduced in plasma of relapsed/refractory NKTCL patients and in chemoresistant cells, inversely correlating with senescence marker SA-β-gal.; LCP2 knockdown enhances chemoresistance, SASP secretion, and G0/G1 cell cycle arrest in NKTCL cells.; LCP2 deficiency activates the IQGAP2/LaminA/C/SUV39H1 axis, driving DNA damage and telomere stress-induced senescence.; Targeting the LCP2-mediated axis with Epitalon and Chaetocin partially eliminates therapy-induced senescent cells and alleviates immunosuppression in vivo.
Epitalon extended telomere length in normal cells through hTERT mRNA and telomerase upregulation.; In cancer cells, telomere lengthening occurred via ALT activation.; ALT activity was minimal in normal cells, indicating cancer-specificity.; Telomere extension was dose-dependent in normal epithelial and fibroblast cells.
High glucose exposure delayed wound healing and increased reactive oxygen species while decreasing antioxidant gene expression in ARPE-19 cells.; High glucose induced epithelial-mesenchymal transition and upregulated fibrosis-related genes, contributing to subretinal fibrosis.; Epitalon reversed the delayed wound healing by inhibiting hyperglycemia-induced EMT and fibrosis.; Epitalon shows promise as a therapeutic strategy for diabetic retinopathy, though further mechanistic and safety studies are needed.
Epitalon exhibits geroprotective and neuroendocrine effects via antioxidant, neuroprotective, and antimutagenic mechanisms.; It directly influences melatonin synthesis and alters interleukin-2 mRNA levels.; The peptide modulates mitogenic activity of murine thymocytes and enhances AChE, BuChE, and telomerase enzyme activity.; Physicochemical and structural studies of Epitalon are limited despite extensive biological research.
Healthy cumulus-oocyte complexes exhibit nuclear telomerase localization, whereas degraded complexes show reduced and cytoplasmic telomerase.; Epitalon treatment significantly improved bovine oocyte maturation rate compared to control (p < 0.05).; Telomerase activity was compromised in post-thawed embryos, but Epitalon significantly improved blastocyst hatching rate and implantation potential (p < 0.05).; Epitalon enhanced quality and health of oocytes, cumulus cells, and post-thawed blastocysts as assessed by qPCR, reactive oxygen species, and JC-1 assays.
Aging is associated with progressive heterochromatinization (condensation of eu- and heterochromatin regions), which can deactivate previously active genes and block normal metabolic processes.; Peptide bioregulators induced unrolling (decondensation) of total heterochromatin and deheterochromatinization of satellite stalks of acrocentric chromosomes, activating ribosomal gene synthetic processes.; The peptides did not cause deheterochromatinization of pericentromeric structural heterochromatin.; Each studied peptide bioregulator (Ala-Glu-Asp-Gly, Lys-Glu-Asp-Ala, Ala-Glu-Asp-Pro, Lys-Glu) had a selective effect on definite chromosome regions, indicating remodeling of facultative heterochromatin.
Frequently asked questions
What is Epitalon?
**Mechanism of Action** Epitalon (Ala-Glu-Asp-Gly) is a synthetic tetrapeptide derived from the pineal gland peptide extract epithalamin. Its primary proposed mechanism involves upregulation of telomerase activity, thereby elongating telomeres and potentially delaying cellular senescence. Additionally, Epitalon is repo
How does Epitalon work?
Khavinson tetrapeptide reported to activate telomerase and normalize pineal melatonin rhythms in aging models.
What is the research status of Epitalon?
Epitalon is currently classified as experimental, with 65 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Epitalon?
Epitalon has a molecular weight of approximately 390.35 g/mol (formula C14H22N4O9).
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