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Epithalon

Also identified as Epitalon, AEDG, Ala-Glu-Asp-Gly

Synthetic tetrapeptide

Sequence: Ala-Glu-Asp-Gly

Molecular weight
390.4
Molecular formula
C14H22N4O9
CAS
307297-39-8
Published studies reviewed
4

FOR RESEARCH USE ONLY. NOT FOR HUMAN OR VETERINARY USE. NOT FOR HUMAN CONSUMPTION.

Compounds described on this site are supplied solely for laboratory research. They are not offered for human or veterinary use or for clinical use, and they are not intended to diagnose, mitigate, cure or prevent any disease.

Epithalon (also written Epitalon or AEDG) is the synthetic tetrapeptide Ala-Glu-Asp-Gly, and it is distinct from epithalamin, a pineal-gland extract whose studies are not included. The four publications reviewed are three cell-culture studies, two on telomeres and telomerase and one on mouse oocytes, plus a lifelong study in mice. Several of the reported results are null, and no human study of the tetrapeptide was identified.

At a glance

Also identified as
Epitalon, AEDG, Ala-Glu-Asp-Gly
Class
Synthetic tetrapeptide
Target or mechanism
The publications recorded here do not identify a receptor or enzyme this peptide binds.
Evidence types represented
in vitro, animal
Published studies reviewed
4
Last reviewed
2026-09-21

Overview

Epithalon is a synthetic four-residue peptide, Ala-Glu-Asp-Gly, also written AEDG and also called Epitalon.

It is not epithalamin. Epithalamin is a polypeptide extract of the pineal gland — a mixture of many molecules — and a large part of the older literature used that extract rather than this tetrapeptide. Studies of the extract are not recorded on this page.

The publications here are four. Two are cell-culture studies of telomeres and telomerase: one from 2003, from the group that originated the compound, and one from 2025 by an independent UK laboratory that measured telomere length, hTERT expression, telomerase activity and an alternative telomere-lengthening pathway side by side, in cancer cell lines and in normal cells. One is a lifelong study in mice. One is an independent in-vitro study of mouse oocytes held in culture after ovulation.

Several of the results below are null: telomerase enzyme activity did not rise significantly in the cancer lines even where its messenger RNA did, and in the mouse study the peptide did not change food consumption, body weight, mean life span or total tumour incidence. Those are printed here as findings, not omitted.

No human study of this tetrapeptide is recorded here, because this project found none.

Mechanism under investigation

The publications recorded here do not identify a receptor or enzyme this peptide binds. Two cell-culture studies report changes downstream: expression of the telomerase catalytic subunit hTERT rose in every cell type tested in the 2025 study, while telomerase enzyme activity rose only in the normal cells and an alternative telomere-lengthening pathway rose only in the cancer lines. A separate in-vitro study of mouse oocytes reports reduced reactive oxygen species and changed mitochondrial measures.

Scope of the published work

Areas investigated
  • Telomere length in cultured cells
  • Telomerase expression and activity
  • Alternative lengthening of telomeres
  • Life span and spontaneous tumour incidence in mice
  • Oocyte quality measures in vitro
Models used
  • Human breast cancer cell lines
  • Normal human fibroblasts and mammary epithelial cells
  • Human fetal fibroblast culture
  • Lifelong study in mice
  • Mouse oocytes in culture

Every figure on this page was recorded in a cell-culture or animal study, using material prepared for that study. It is not the research material PepGenex supplies and no result here transfers to it, or to a person.

Limitations

Evidence represented on this page: in vitro and animal. No human research is represented. The page reviews 4 published studies, and each figure is reported for the study that published it; results are not pooled across studies.

Common questions

What is Epithalon?

Epithalon is a synthetic four-residue peptide, Ala-Glu-Asp-Gly, also written AEDG and also called Epitalon.

How does Epithalon work, according to the published research?

The publications recorded here do not identify a receptor or enzyme this peptide binds. Two cell-culture studies report changes downstream: expression of the telomerase catalytic subunit hTERT rose in every cell type tested in the 2025 study, while telomerase enzyme activity rose only in the normal cells and an alternative telomere-lengthening pathway rose only in the cancer lines. A separate in-vitro study of mouse oocytes reports reduced reactive oxygen species and changed mitochondrial measures.

  • Reports that adding Epithalon peptide to a telomerase-negative human fetal fibroblast culture induced expression of the catalytic subunit of telomerase, enzymatic activity of telomerase, and telomere elongation. The abstract prints no concentration, no duration and no measured value. (Khavinson et al., 2003, PMID 12937682)

What has published research on Epithalon found, and what are its limits?

This page records 4 publications, reporting laboratory (in vitro) work in 3, animal work in 1. Each is listed with its identifier under References.

No human study is represented on this page.

Evidence represented on this page: in vitro and animal.

No human research is represented.

The page reviews 4 published studies, and each figure is reported for the study that published it; results are not pooled across studies.

Every figure on this page was recorded in a cell-culture or animal study, using material prepared for that study. It is not the research material PepGenex supplies and no result here transfers to it, or to a person.

Is Epithalon approved by the U.S. FDA?

This page cites no FDA approval record for Epithalon; PepGenex Science states a U.S. regulatory status only where a sourced record exists.

PepGenex research materials are not FDA approved and are not for human or veterinary use.

What risks have published studies of Epithalon reported?

No human study is recorded on this page, so it reports no adverse events in people. Laboratory and animal findings are not a measure of risk in people.

Published research

Grouped by the kind of study. Select one to narrow what is shown below.

Laboratory (in vitro)(3)

Laboratory (in vitro)

Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity.

Al-dulaimi S, Thomas R, Matta S, Roberts T., Biogerontology, 2025;26(5):178

published; corrected (Biogerontology 2025;27:1)

Breast cancer cell lines 21NT and BT474 were exposed to epitalon at four ascending concentrations for 4 days; normal fibroblasts (IBR.3) and mammary epithelial cells (HMEC) were exposed to the highest of those concentrations for 3 weeks. Untreated cells served as the baseline control. Telomere length was measured by qPCR, hTERT messenger RNA by RT-qPCR, telomerase activity by the telomere repeat amplification protocol, and alternative lengthening of telomeres by the c-circle assay with immunofluorescence for PML bodies.

hTERT messenger RNA expression, relative to untreated cells
Day 4 · Cultured human breast cancer cell line 21NT · vs Untreated control cells
ArmReported
Epitalon (highest concentration)12-fold
hTERT messenger RNA expression, relative to untreated cells
Day 4 · Cultured human breast cancer cell line BT474 · vs Untreated control cells
ArmReported
Epitalon (second-highest concentration)fivefold
Telomerase enzyme activity, relative to untreated cells
Week 3 · Cultured normal human fibroblasts (IBR.3) · vs Untreated control cells
ArmReported
Epitalon (highest concentration)fourfold
Telomerase enzyme activity, relative to untreated cells
Week 3 · Cultured normal human mammary epithelial cells (HMEC) · vs Untreated control cells
ArmReported
Epitalon (highest concentration)26-fold
  • In both cancer lines, 4 days of exposure was associated with a concentration-dependent increase in telomere length from the second-lowest concentration up to the highest. At the lowest concentration, the authors report a decrease in telomere length in 21NT and a lower rate of elongation in BT474. In BT474 the maximum length was reached at the second-lowest concentration, with less elongation at the two higher concentrations. In the normal cells, no increase was seen after 4 days at the highest concentration (reported as data not shown), while 3 weeks at the same concentration gave a significant increase in both IBR.3 and HMEC against untreated controls.
  • In the same cancer lines, 4 days at the two highest concentrations did not lead to a significant increase in telomerase enzyme activity compared with the untreated controls. The authors note that although telomere length and hTERT expression were elevated, telomerase activity did not follow the same pattern.
  • Alternative lengthening of telomeres, measured by the c-circle assay after 4 days at the highest concentration, was ten-fold higher in 21NT and threefold higher in BT474 than in untreated cells, and immunofluorescence showed a significant elevation of PML bodies in both. In the normal cells, IBR.3 showed no increase in this activity and HMEC showed an increase the authors describe as insignificant.
Context

The 2025 study found the messenger RNA for the telomerase catalytic subunit rose in every cell type it tested, but the enzyme's activity rose only in the normal cells; in the two cancer lines it did not separate from the untreated controls, and the telomere lengthening there tracked a different pathway instead. A measurement of gene expression is not a measurement of enzyme activity, and this study is where the two part company.

View publication →
Laboratory (in vitro)

Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro.

Yue X, Liu SL, Guo JN, Meng TG, Zhang XR, Li HX, Song CY, Wang ZB, Schatten H, Sun QY, Guo XP., Aging (Albany NY), 2022;14(7):3191-3202

published

Epitalon at 0.1 mM was added to the culture medium of mouse oocytes held in culture after ovulation, and oocyte quality measures were evaluated at 6, 12 and 24 hours of culture.

  • At 0.1 mM, the peptide reduced intracellular reactive oxygen species. The authors report that it significantly decreased the frequency of spindle defects and of abnormal distribution of cortical granules during aging for 12 h and 24 h, while increasing mitochondrial membrane potential and mitochondrial DNA copy number. No numeric value for any of these measures is printed in the abstract.
  • Apoptosis of the oocytes was decreased by 24 hours of culture. The authors' stated conclusion is that the peptide can delay the aging process of oocytes in vitro by way of mitochondrial activity and reactive oxygen species levels.
View publication →
Laboratory (in vitro)

Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells.

Khavinson VKh, Bondarev IE, Butyugov AA., Bulletin of Experimental Biology and Medicine, 2003;135(6):590-592

published

  • Reports that adding Epithalon peptide to a telomerase-negative human fetal fibroblast culture induced expression of the catalytic subunit of telomerase, enzymatic activity of telomerase, and telomere elongation. The abstract prints no concentration, no duration and no measured value.
Limitations

Much of the published work on this tetrapeptide comes from one group — the St Petersburg institute that originated it — and the two oldest records on this page are theirs. The 2003 cell-culture report prints no concentration, no duration and no measured value at all. Two of the four publications here are independent of that group, and they are the ones carrying figures.

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Preclinical (animal)(1)

Preclinical (animal)n = 108

Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice.

Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, Alimova IN, Rosenfeld SV, Zavarzina NY, Semenchenko AV, Yashin AI., Biogerontology, 2003;4(4):193-202

published

From the age of 3 months until their natural deaths, female outbred Swiss-derived SHR mice received either normal saline (control) or the tetrapeptide Epitalon (Ala-Glu-Asp-Gly) in saline, given in repeated courses. There were 54 mice in each group.

  • The peptide did not influence food consumption, body weight or mean life span, and did not influence total spontaneous tumour incidence, compared with the control group.
  • Against the same control group, the authors report that the peptide slowed the age-related switching-off of oestrous function and decreased the frequency of chromosome aberrations in bone marrow cells by 17.1% (P < 0.05).
Limitations

In the lifelong mouse study, the measures that did not move are as much the result as the ones that did: no change in food consumption, in body weight, in mean life span, or in how many mice developed a tumour at all. The figures that did change are reported above with the authors' own p-values, in mice, on a monthly schedule chosen for that study.

View publication →

References

Published studies reviewed (4)

  1. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. — Khavinson VKh, Bondarev IE, Butyugov AA., Bulletin of Experimental Biology and Medicine, 2003;135(6):590-592
    DOI 10.1023/a:1025493705728 · PMID 12937682
  2. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. — Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, Alimova IN, Rosenfeld SV, Zavarzina NY, Semenchenko AV, Yashin AI., Biogerontology, 2003;4(4):193-202
    DOI 10.1023/a:1025114230714 · PMID 14501183
  3. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. — Al-dulaimi S, Thomas R, Matta S, Roberts T., Biogerontology, 2025;26(5):178
    DOI 10.1007/s10522-025-10315-x · PMID 40908429 · PMC12411320
  4. Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro. — Yue X, Liu SL, Guo JN, Meng TG, Zhang XR, Li HX, Song CY, Wang ZB, Schatten H, Sun QY, Guo XP., Aging (Albany NY), 2022;14(7):3191-3202
    DOI 10.18632/aging.204007 · PMID 35413689 · PMC9037278

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