# Epitalon - Canonical: https://residue.info/c/epitalon/ - Also called: Epithalon, Epithalone, AEDG peptide, Ala-Glu-Asp-Gly - Evidence grade: C (Limited / early human data). Human data are limited to an uncontrolled clinical report; the substantive evidence is cellular and murine. - Status: Not FDA-approved · FDA compounding nomination withdrawn - PubChem CID: 219042 - Updated: 2026-10-19 · Reviewed by: Residue Editorial Team Epitalon (also spelled epithalon) is the synthetic tetrapeptide Ala-Glu-Asp-Gly, designed from the amino-acid composition of epithalamin, a bovine pineal-gland extract [1]. In human cell lines it lengthened telomeres by up-regulating telomerase [2], and in HER-2/neu transgenic mice it extended average lifespan by 13.5% [3]. Human evidence is limited to uncontrolled reports, and it is not FDA-approved [4]. ## Key findings - Epitalon was synthesized based on the amino-acid composition of epithalamin, a bovine pineal extract [1]. (anchor: https://residue.info/c/epitalon/#kf-pmid-40141333) - In normal human epithelial and fibroblast cells, it produced dose-dependent telomere lengthening via hTERT and telomerase up-regulation; in breast-cancer cell lines, lengthening occurred through ALT activation [2]. (anchor: https://residue.info/c/epitalon/#kf-pmid-40908429) - In female HER-2/neu transgenic mice, 1 mg five times weekly extended mean lifespan by 13.5% and maximum by 13.9%, and reduced breast adenocarcinomas [3]. (anchor: https://residue.info/c/epitalon/#kf-pmid-12459848) - A 2002 report claimed a positive clinical effect in 90% of patients with degenerative retinal lesions, without a described control group [5]. (anchor: https://residue.info/c/epitalon/#kf-pmid-12195242) - ClinicalTrials.gov lists no registered study [6]; FDA lacks sufficient information to know whether it would cause harm in humans [4]. (anchor: https://residue.info/c/epitalon/#kf-ctgov-epitalon) ## Effects by system - Telomeres (cells) (grade D): Telomere extension via telomerase in normal cells, via ALT in cancer cell lines [2]. (anchor: https://residue.info/c/epitalon/#effect-telomeres-cells) - Lifespan and tumors (mice) (grade D): Longer lifespan and fewer breast tumors in HER-2/neu mice [3]; fewer malignant tumors and no metastases in C3H/He mice [7]. (anchor: https://residue.info/c/epitalon/#effect-lifespan-and-tumors-mice) - Retina (grade C): Uncontrolled report of benefit in retinitis pigmentosa patients; rat retinal function preserved [5]. (anchor: https://residue.info/c/epitalon/#effect-retina) ## What is epitalon? Epitalon is the tetrapeptide Ala-Glu-Asp-Gly (AEDG), designed from the amino-acid composition of epithalamin, an extract of bovine pineal gland, before AEDG itself was found in pineal polypeptide preparations [1]. Figure 1 shows its four residues from PubChem [8]. ## How is Epitalon thought to work? A 2025 review lists reported effects on melatonin synthesis, interleukin-2 mRNA, thymocyte mitogenic activity and enzymes including telomerase, while concluding that it remains uncertain whether these are its sole mechanisms. The same review notes that physico-chemical and structural studies of the peptide are quite limited [1]. The best-quantified mechanism is telomere maintenance. In normal epithelial and fibroblast cells, epitalon extended telomere length in a dose-dependent manner through up-regulation of hTERT mRNA and telomerase activity. In the breast-cancer lines 21NT and BT474, telomeres also lengthened, but through Alternative Lengthening of Telomeres (ALT) — an ALT effect the authors found to be specific to the cancer cells [2]. ## What have studies found? **Mice.** In female HER-2/neu transgenic mice given 1 mg subcutaneously five times a week from the second month of life, mean and maximum lifespan rose 13.5% and 13.9%; breast adenocarcinomas, lung metastases and multiple tumors were reduced [3]. In one-year-old female C3H/He mice, 0.1 µg five times weekly for 6.5 months reduced the number with malignant tumors, and no metastases were found versus 3 of 9 tumor-bearing controls [7]. **Humans.** A 2002 paper reported that in Campbell rats epitalon preserved retinal structure and function, and that in patients with degenerative retinal lesions it produced "a positive clinical effect in 90% of the cases" [5]. The abstract gives no control group, patient numbers or outcome measures. ClinicalTrials.gov lists no registered epitalon study [6]. FDA lists epitalon among withdrawn compounding nominations, noting possible immunogenicity from aggregation and peptide-related impurities, and that it has not identified safety-related information for the proposed route — so it lacks sufficient information to know whether the drug would cause harm in humans [4]. ## What is still unknown? - **Controlled human studies** of any outcome, published with full methods. - **The cancer-cell telomere finding** needs reconciling with anti-tumor claims from mouse studies [2][3]. ## Frequently asked questions **Is epitalon the same as epithalon?** Yes — the same tetrapeptide, Ala-Glu-Asp-Gly, also spelled epithalone [1]. **Does epitalon lengthen telomeres?** In cell lines, yes: a 2025 study found dose-dependent telomere lengthening in normal cells via telomerase, and in cancer cells via the ALT pathway [2]. That study used cultured cells, not people. **Does epitalon extend lifespan?** In one transgenic mouse strain prone to breast cancer, mean lifespan rose 13.5% [3]. There are no human lifespan data. **Is epitalon FDA-approved?** No. FDA lists epitalon among withdrawn compounding nominations and says it lacks sufficient information to know whether it would cause harm in humans [4]. **Is epitalon safe?** Unknown in humans. In mice, long-term low doses showed no toxic effect [7], but FDA notes immunogenicity risk and no identified safety information for proposed routes [4]. ## Sources [1] Overview of Epitalon-Highly Bioactive Pineal Tetrapeptide with Promising Properties. Araj SK et al. Int J Mol Sci. 2025. https://pubmed.ncbi.nlm.nih.gov/40141333/ [2] Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Al-Dulaimi S et al. Biogerontology. 2025. https://pubmed.ncbi.nlm.nih.gov/40908429/ [3] Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice. Anisimov VN et al. Bull Exp Biol Med. 2002. https://pubmed.ncbi.nlm.nih.gov/12459848/ [4] Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks [5] Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa. Khavinson V et al. Neuro Endocrinol Lett. 2002. https://pubmed.ncbi.nlm.nih.gov/12195242/ [6] ClinicalTrials.gov registry search: epitalon OR epithalon. 0 registered studies at fetch. https://clinicaltrials.gov/search?intr=epitalon%20OR%20epithalon [7] Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. Kossoy G et al. In Vivo. 2006. https://pubmed.ncbi.nlm.nih.gov/16634527/ [8] PubChem compound record: Epitalon. C14H22N4O9 · MW 390.35 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/219042 --- From Residue. Research and education only; not medical advice. Quote with attribution and a link to the canonical page.