Epithalon product image

Epithalon

Alternative names
Epitalon, Epithalone, AE-0 peptide
CAS
307297-39-8
Molecular formula
C14H22N4O9
Molecular weight
390.35
Amino acid sequence
Ala-Glu-Asp-Gly
Size:
109 

This product is intended exclusively for research and laboratory purposes (in vitro). It is not intended for diagnostic, therapeutic, food, cosmetic, veterinary or supplement use.

Purchases may be made only by adults. The buyer confirms appropriate knowledge and qualifications for safe handling of research chemicals.

Product description

What is Epithalon?

Epithalon (also known as Epitalon or AEDG) is a synthetic tetrapeptide with the Ala-Glu-Asp-Gly sequence, which is a functional analog of the natural pineal peptide Epithalamine. This compound was developed in the early 2000s by Professor Vladimir Khavinson at the Institute of Bioregulation and Gerontology in Saint Petersburg as part of a broader research program on regulatory peptides and aging processes.

The history of Epithalon goes back to research on pineal extracts conducted in the Soviet Union since the 1970s. Scientists observed that administering pineal extract to aging animals led to improved health parameters and extended lifespan. Later work made it possible to identify the active component — the AEDG tetrapeptide — which was then synthesized as Epithalon.

Structurally, Epithalon is one of the smallest biologically active peptides, consisting of just four amino acids linked by α-peptide bonds. Its molecular weight is about 390 Da, which allows it to directly interact with DNA and act as a regulatory factor in gene expression. In 2017, endogenous Epithalon was detected for the first time in a physiological human pineal extract, confirming its natural occurrence in the body.

The pineal gland, which is the site of Epithalon synthesis, plays a key role in regulating circadian rhythms through melatonin production. With age, pineal function declines, leading to reduced synthesis of both melatonin and endogenous regulatory peptides. Epithalon is being studied as a potential factor supporting neuroendocrine functions in the aging process.

Mechanism of action

Telomerase activation — Epithalon induces expression of the catalytic subunit of telomerase (hTERT), the enzyme responsible for telomere elongation. Studies in human fibroblasts showed that the peptide increases both hTERT mRNA levels and telomerase enzymatic activity, leading to measurable telomere elongation in somatic cells.

Regulation of melatonin synthesis — Epithalon directly affects melatonin production by the pineal gland, restoring the physiological rhythm of its secretion in aging individuals. This mechanism involves modulation of genes associated with the circadian rhythm and an effect on the hypothalamic-pituitary axis.

Antioxidant action — The peptide increases the activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase. This leads to a reduction in oxidative stress and protection of DNA against damage caused by reactive oxygen species.

Modulation of mitochondrial function — Studies from 2025 showed that Epithalon improves mitochondrial health by increasing the expression of the PGC-1α, SIRT-1, TFAM and BCL2 genes. The peptide reduces intracellular levels of reactive oxygen species and supports proper mitochondrial structure.

Effect on gene expression — Epithalon interacts with histone H1, modulating chromatin structure and gene accessibility to the transcriptional machinery. This may lead to epigenetic regulation of gene expression related to aging and cellular differentiation.

Directions of scientific research

Research on Epitalon focuses on its potential impact on cellular aging processes, neuroendocrine functions, and protection against DNA damage.

Telomere elongation and telomerase activation

In a landmark 2003 study, Khavinson and colleagues showed that adding Epithalon to cultures of human fetal fibroblasts, originally lacking telomerase activity, induced hTERT expression and telomere elongation. Peptide-treated cells exceeded the Hayflick limit, continuing to divide beyond the normal point of replicative senescence. A 2025 study (Al-dulaimi et al.) confirmed these observations, documenting a dose-dependent increase in telomere length in normal epithelial cells and fibroblasts through hTERT upregulation.

Longevity research

In rodent experiments, Epithalon extended the lifespan of mice and rats, especially those predisposed to accelerated aging or a high risk of tumors. A prospective cohort study of 266 people over 60 found that treatment with Epithalamin (the pineal extract from which Epithalon is derived) reduced mortality 1.6- to 1.8-fold over 6 years of follow-up, and in combination with Thymalin — 2.5-fold.

Neuroendocrine functions and melatonin

Studies in aging monkeys and humans showed that Epithalon restores pineal melatonin secretion to levels characteristic of younger individuals. In clinical studies, patients aged 60-80 receiving the peptide showed normalization of the circadian melatonin rhythm and improved sleep quality.

Protection against DNA damage

In a study of patients with pulmonary tuberculosis, Epithalon did not correct existing chromosomal aberrations, but it showed a protective effect against the formation of new damage. In neuroblastoma cells, the peptide reduced levels of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage.

Reproductive functions and embryology

A 2025 study (Ullah et al.) showed that Epithalon stimulates telomerase activity in bovine cumulus cells and cumulus-oocyte complexes, accelerating oocyte maturation by improving mitochondrial health. Peptide therapy significantly improved embryo expansion and hatching rates after thawing.

Scientific context

Epithalon belongs to the class of bioregulatory peptides developed within the Russian aging research program. Related compounds include:

  • Thymalin — a thymic peptide supporting immune functions
  • Cortexin — a cerebral cortex peptide with neuroprotective effects
  • Retinalamin — a retinal peptide used in eye diseases

Compared with other approaches to telomerase activation, Epithalon stands out for its structural simplicity and good bioavailability. Unlike gene therapy or HDAC inhibitors, the peptide acts directly at the level of hTERT transcription without genome modification.

For 25 years since the patenting of its synthesis, Epithalon has been the subject of numerous in vitro, in vivo, and in silico studies. Despite statistically significant geroprotective and neuroendocrine effects, the exact mechanism of action remains unclear. The peptide is approved for clinical use in Russia, but it does not have FDA or EMA registration.

Safety profile in studies

General tolerability — In Russian clinical studies conducted over more than 30 years, Epithalon has shown a good safety profile. No serious adverse events causally linked to peptide administration were reported.

Adverse effects — Rarely observed side effects include: anxiety, vivid dreams, fatigue or mild euphoria, headaches and dizziness, changes in sleep patterns, and local reactions at the injection site (redness, swelling).

Theoretical concerns — Due to the telomerase activation mechanism, there are theoretical concerns about a potential promotion of tumor growth. However, studies in mice showed that Epithalon reduced the incidence of spontaneous tumors 2.6-fold and displayed oncostatic and antimetastatic properties. Nevertheless, caution is recommended in people with active cancer.

Regulatory status — Epithalon is not approved by the FDA or EMA for clinical use. In Russia it has been used in clinical practice since the 1990s. In December 2023, the FDA expressed safety concerns related to certain peptide substances nominated for compounding, including in the context of telomerase activators.

Bibliography – latest scientific research

  1. Araj SK et al. Overview of Epitalon—Highly Bioactive Pineal Tetrapeptide with Promising Properties. Int J Mol Sci. 2025;26(6):2691. PubMed
  2. Al-dulaimi S et al. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology. 2025;26(1):27. PubMed
  3. Ullah S et al. Epitalon-activated telomerase enhance bovine oocyte maturation rate and post-thawed embryo development. Life Sci. 2025;361:123291. PubMed
  4. Gatta M et al. The Antioxidant Tetrapeptide Epitalon Enhances Delayed Wound Healing in an in Vitro Model of Diabetic Retinopathy. Stem Cell Rev Rep. 2025;21(2):567-580. PubMed
  5. Ivko OM et al. Peptidergic regulation of expression of cellular aging marker proteins in buccal epithelium. Adv Gerontol. 2024;37(3):211-218. PubMed
  6. Yue X et al. Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro. Aging. 2022;14(7):3191-3202. PubMed
  7. Khavinson VK et al. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003;135(6):590-592. PubMed
  8. Anisimov VN et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology. 2003;4(4):193-202. PubMed
  9. Kraskovskaya NA et al. The effect of AEDG peptide on neuronal differentiation and neurite outgrowth. Bull Exp Biol Med. 2024;176(4):469-473. PubMed
  10. Avolio F et al. Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line. Int J Mol Sci. 2022;23(7):3607. PubMed
This site is registered on wpml.org as a development site. Switch to a production site key to remove this banner.