Epithalon [Peptide]

Description

What is Epithalon (Epitalon)?

Epithalon, also known as Epitalon or Epithalone, is a synthetic tetrapeptide composed of four amino acids — alanine, glutamic acid, aspartic acid, and glycine — with the sequence Ala-Glu-Asp-Gly (AEDG). The compound was first developed by Professor Vladimir Khavinson and colleagues at the Saint Petersburg Institute of Bioregulation and Gerontology, Russia. Its sequence is derived from the amino acid composition of Epithalamin, a polypeptide complex extracted from bovine pineal gland tissue, which the Khavinson group proposed as the active component responsible for Epithalamin’s observed bioregulatory effects in preclinical models. Epithalamin was first characterised in the 1970s as part of a broader programme of pineal gland peptide bioregulation research; Epithalon was subsequently synthesised as a defined tetrapeptide to investigate these effects in controlled experimental systems.

Epithalon has been investigated for approximately three decades, primarily in the laboratory of Khavinson and collaborators at the Saint Petersburg Institute. The compound has been studied in rodent in vivo models, isolated cell preparations, and limited human studies for its potential interactions with telomerase activity, telomere length regulation, pineal gland neuroendocrine function, and cellular ageing processes. Researchers and reviewers outside the primary research group have noted that the majority of published Epithalon literature originates from a single research centre, and that independent multi-centre replication of key findings is limited — a context researchers should account for when evaluating the evidence base.

Epithalon is not approved by the Food and Drug Administration for human or veterinary use. It is not a dietary supplement and is not intended for human consumption or therapeutic self-administration. All RCDbio research compounds are supplied strictly for laboratory and research purposes only.

Chemical Properties

Property	Detail
Product Type	Synthetic Tetrapeptide / Pineal Gland-Derived Peptide Bioregulator
Product Name	Epithalon (Epitalon)
Application	Scientific / Research Use Only
CAS Number	307297-39-8
Molar Mass	390.349 g/mol
Chemical Formula	C14H22N4O9
PubChem CID	219042
IUPAC Name	(4S)-4-[[(2S)-2-aminopropanoyl]amino]-5-[[(2S)-3-carboxy-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
Amino Acid Sequence	Ala-Glu-Asp-Gly (AEDG); 4 amino acids; free N-terminus; free C-terminus
Parent Peptide Complex	Epithalamin — bovine pineal gland polypeptide extract from which the AEDG sequence was identified
Synonyms	Epitalon; Epithalone; AEDG peptide; H-Ala-Glu-Asp-Gly-OH; L-alanyl-L-glutamyl-L-aspartylglycine
Physical Form	Lyophilized white to off-white powder
Solubility	Freely soluble in water; soluble in PBS and standard aqueous buffers
Storage (Lyophilized)	−20°C; sealed container; protected from light and moisture
Storage (Reconstituted)	4°C; use within 48–72 hours; avoid repeated freeze-thaw cycles
Purity	≥98% (HPLC verified, independent third-party laboratory analysis)
WADA Status	Epithalon is not explicitly named on the 2026 WADA Prohibited List. As a non-approved synthetic peptide with reported neuroendocrine and cellular ageing pathway activity, S0 (Non-Approved Substances) provisions may apply in sport-adjacent research contexts. Verify at GlobalDRO.com before use.

How Does Epithalon Work?

Epithalon’s proposed mechanisms are derived primarily from studies conducted by the Khavinson research group and a limited number of independent investigators. The mechanisms below are presented as preclinical observations and hypotheses, acknowledging that independent multi-centre replication is limited for many reported findings.

Telomerase Activation and hTERT Upregulation

The foundational reported mechanism for Epithalon is the induction of telomerase activity in human somatic cell preparations. In the 2003 study by Khavinson, Bondarev, and Butyugov, exposure of human fetal fibroblasts to Epithalon was associated with increased expression of the telomerase catalytic subunit (hTERT), upregulated enzymatic activity of telomerase, and measurable elongation of telomere length compared to untreated control cells [Khavinson et al., 2003]. Telomeres are repetitive DNA sequences (TTAGGG) at chromosome ends that shorten progressively with cell division; telomerase adds telomeric repeats to counteract this shortening, but its activity is silenced in most human somatic cells. The hypothesis that Epithalon reactivates telomerase in somatic cells has been the central focus of subsequent Epithalon research. A 2025 cell-line study by Al-dulaimi et al. investigated Epithalon in normal epithelial cells, fibroblasts, and breast cancer cell lines, characterising both hTERT-mediated telomerase upregulation and ALT (alternative lengthening of telomeres) pathway engagement across different cell types [Al-dulaimi et al., 2025].

DNA-Binding and Chromatin Regulation

In molecular modelling and in vitro binding studies, the AEDG tetrapeptide has been proposed to bind directly to DNA double-strand sequences, particularly TTAGGG telomeric repeat units, through electrostatic and hydrogen bonding interactions. In silico docking studies suggest that Epithalon may interact with the major groove of double-stranded DNA, influencing chromatin accessibility and gene expression patterns. In a 2020 study examining neurogenesis models, Khavinson et al. characterised Epithalon-associated changes in gene expression and protein synthesis patterns in neural differentiation preparations, proposing an epigenetic regulatory mechanism [Khavinson et al., 2020].

Pineal Gland and Neuroendocrine Pathway Interactions

In aged rodent in vivo models, Epithalon administration has been associated with changes in pineal gland function, including melatonin secretion pattern restoration and neuroendocrine axis modulation. Research in animals subjected to disrupted light-dark cycle conditions examined Epithalon’s effects on the circadian-neuroendocrine interface, with observed associations between Epithalon treatment and altered thyroid hormone, gonadotropin, and corticosteroid secretion patterns in aged rodent preparations. These findings relate to the original epithalamin bioregulation hypothesis — that the pineal gland produces regulatory peptides that modulate neuroendocrine ageing processes.

Antioxidant and Mitochondrial Pathway Interactions

In isolated cell and rodent model preparations, Epithalon has been associated with the reduction of reactive oxygen species (ROS) markers, improved mitochondrial membrane potential, and increased mitochondrial DNA copy number in oocyte and cell culture systems. These findings have been primarily characterised in the context of oocyte ageing and post-ovulatory ageing models in rodent and bovine preparations.

Key Research Findings

In preclinical and limited in vitro research contexts, Epithalon has been associated with the following observations. The majority of published findings originate from a single research group; independent multi-centre replication is limited.

• Telomerase induction in human somatic cells: Increased hTERT expression, upregulated telomerase activity, and measurable telomere elongation observed in human fetal fibroblast preparations exposed to Epithalon in the foundational 2003 study [Khavinson et al., 2003].
• Extended lifespan in Drosophila: Epithalon administration associated with 16% increase in mean lifespan and 11% increase in maximum lifespan in Drosophila melanogaster models [Khavinson et al., 2000; PMID 11087911].
• SHR mouse biomarkers: In female SHR mice, Epithalon was associated with improved biomarkers of ageing, reduced spontaneous tumour incidence, and extended lifespan relative to controls [Anisimov et al., 2003].
• 2025 cell-line telomere study: Al-dulaimi et al. characterised dose-dependent hTERT upregulation and ALT pathway engagement across normal and cancer cell line preparations, providing the most methodologically detailed Epithalon telomere study to date [Al-dulaimi et al., 2025].
• Neurogenesis gene expression: Epithalon is associated with stimulated gene expression and protein synthesis markers during neural differentiation in cell model preparations; an epigenetic regulatory mechanism is proposed [Khavinson et al., 2020].

All findings listed above are derived from preclinical in vitro and in vivo data and limited early-phase human observations. The majority originates from a single research group. No regulatory-grade human clinical trial data have been established for Epithalon. Independent multi-centre replication of key findings is limited. These observations do not constitute evidence of efficacy or safety in any human condition or organism.

What are the Potential Research Applications of Epithalon?

In controlled laboratory environments, Epithalon has been investigated for the following research applications. These are observed in preclinical and in vitro contexts only and do not constitute claims of efficacy or safety in any organism.

Telomerase Activity and Telomere Biology Research Epithalon is employed as a reference compound in studies examining telomerase activity induction, hTERT expression modulation, and telomere length dynamics in human and animal cell culture systems. Research employs TRAP assays, qPCR hTERT quantification, FISH telomere length measurement, and flow cytometry in both normal and cancer cell line preparations.

Cellular Ageing and Senescence Pathway Studies. In primary human cell cultures and aged rodent tissue preparations, Epithalon is investigated for its effects on cellular senescence markers, p21/p53 pathway expression, ROS accumulation, and DNA damage response signalling. Research examines the relationship between peptide-mediated telomerase modulation and downstream senescence pathway attenuation.

Pineal Gland Neuroendocrine Research In aged rodent in vivo models, Epithalon is investigated for its effects on pineal gland secretory function, melatonin production patterns, and downstream neuroendocrine axis interactions. Research examines the relationship between AEDG peptide administration and circadian-neuroendocrine regulatory pathway modulation.

Mitochondrial Biology and Oocyte Ageing Studies. In post-ovulatory oocyte ageing models and isolated mitochondrial preparations, Epithalon is investigated for effects on mitochondrial membrane potential, ROS production, mitochondrial DNA copy number, and spindle morphology under oxidative stress conditions. These applications are relevant to fertility research and cellular quality maintenance research in controlled laboratory systems.

Epigenetic Regulation and Gene Expression Studies Based on the proposed DNA-binding mechanism and the 2020 neurogenesis data, Epithalon is investigated in chromatin accessibility assays, ChIP-seq experiments, and RNA-seq profiling to characterise its effects on gene expression programs in neural differentiation and cell specification models.

What are the Potential Side Effects of Epithalon?

Researchers in preclinical and in vitro settings have noted the following observations. Human safety data is extremely limited.

• Generally low acute toxicity profile reported in rodent preclinical studies at doses used in ageing and telomere research; no significant adverse effects reported in published preclinical studies at research-relevant concentrations
• No carcinogenic or tumour-promoting effects observed in long-term rodent studies at research doses; Epithalon-treated animals showed reduced spontaneous tumour incidence in Khavinson group studies — though independent carcinogenicity data is absent
• Telomerase activation in somatic cells raises a theoretical consideration for cancer biology research contexts: telomerase reactivation is also observed in cancer cells as a mechanism of immortalisation; the implications for Epithalon’s effects on cancer cell lines versus normal cells have been investigated, but not uniformly characterised
• No human safety or tolerability data have been established for Epithalon. These observations are derived from experimental systems and should not be extrapolated to human or animal outcomes.

Risk & Handling

Handling Precautions

Epithalon should only be handled by trained laboratory personnel. Appropriate PPE is required: nitrile gloves, a laboratory coat, and eye protection at a minimum. When working with lyophilized powder, use within a laminar flow cabinet or a clean area. Avoid aerosol generation during reconstitution.

Exposure Risks

Risk Tier: LOW

Epithalon has demonstrated a low acute toxicity profile in published preclinical rodent studies at research-relevant doses. No significant adverse effects have been reported at concentrations used in ageing and telomere biology research. The compound’s proposed telomerase-activating activity in somatic cell preparations is a relevant pharmacological consideration for laboratory risk assessment in cell biology experimental contexts. No human safety or tolerability data have been established for Epithalon.

Storage

• Lyophilized form: Store at −20°C in original sealed, light-protected container with desiccant
• Reconstituted form: Store at 4°C; use within 48–72 hours of reconstitution
• Do not subject to repeated freeze-thaw cycles; tetrapeptide integrity may be compromised
• Protect from prolonged light exposure and moisture

Frequently Asked Questions

Q: What is Epithalon, and what is it investigated for in research? A: Epithalon (Epitalon; AEDG) is a synthetic tetrapeptide derived from the amino acid composition of the bovine pineal gland peptide complex Epithalamin. It is investigated in preclinical and in vitro research contexts for telomerase activity induction, telomere length regulation, pineal gland neuroendocrine pathway interactions, and cellular ageing pathway modulation. The majority of published research originates from the Khavinson group at the Saint Petersburg Institute. It is not approved by the FDA for human use and is intended strictly for laboratory and research purposes.

Q: What is the evidence for Epithalon’s effect on telomere length? A: The primary evidence comes from the Khavinson et al. 2003 study (PMID 12937682), which reported hTERT upregulation and telomere elongation in human fetal fibroblast preparations. A 2025 cell-line study (Al-dulaimi et al., Biogerontology) provided more detailed characterisation of dose-dependent hTERT upregulation and ALT pathway engagement. The total body of evidence is limited in volume and independent replication; the majority of findings originate from one research centre. Researchers should account for this when designing studies and interpreting existing data.

Q: What is the difference between Epithalon, Epithalamin, and N-Acetyl Epithalon Amidate? A: Epithalamin is a natural bovine pineal gland polypeptide complex extract containing multiple peptides. Epithalon (AEDG) is the synthetic tetrapeptide derived from the amino acid composition of Epithalamin and proposed as its active component. N-Acetyl Epithalon Amidate is a terminally modified version of Epithalon with N-terminal acetylation and C-terminal amidation added to increase metabolic stability by protecting against exopeptidase degradation — analogous to the relationship between Semax and N-Acetyl Semax Amidate.

Q: What is the half-life of Epithalon in preclinical models? A: Specific standardised pharmacokinetic half-life data for Epithalon in plasma are limited in published peer-reviewed literature. As a free tetrapeptide without terminal protection, Epithalon is expected to be susceptible to aminopeptidase and carboxypeptidase degradation in biological matrices. The AEDG sequence’s compact structure may provide some inherent stability. Precise half-life characterisation in standardised rodent plasma assays is not available in the published literature as of this writing.

Q: How should Epithalon be stored? A: Lyophilized Epithalon should be stored at −20°C in a sealed, light-protected container with desiccant. Once reconstituted, store at 4°C and use within 48–72 hours. Repeated freeze-thaw cycles are not recommended as they may compromise peptide integrity.

Q: What toxicity observations have been reported for Epithalon in preclinical studies? A: Published preclinical rodent studies in the Khavinson research programme have not reported significant toxicity at research-relevant doses. Long-term rodent studies reported reduced spontaneous tumour incidence in treated versus control animals; independent carcinogenicity characterisation across multiple research centres is absent. No human safety or tolerability data have been established. These observations should not be extrapolated to human or animal outcomes.

Related Research Compounds

Researchers investigating Epithalon may also be interested in the following compounds currently available for laboratory research at RCDbio:

• Humanin — A mitochondria-derived 24-amino acid peptide investigated for anti-apoptotic Bax inhibition and neuroprotective STAT3 pathway activation; shares the mitochondrial biology and cellular longevity research context with Epithalon.
• DSIP — A synthetic neuroendocrine nonapeptide investigated for pineal gland-adjacent neuroendocrine HPA axis pathway research; shares the neuroendocrine and circadian biology research context with Epithalon.

All products listed are for laboratory and research purposes only.

References

1. Khavinson, V. K., Bondarev, I. E., & Butyugov, A. A. (2003). Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bulletin of Experimental Biology and Medicine, 135(6), 590–592. https://pubmed.ncbi.nlm.nih.gov/12937682/
2. Anisimov, V. N., Khavinson, V. Kh., Provinciali, M., Viticchi, C., Franceschi, C., & Mikheev, V. S. (2003). Effect of Epitalon on biomarkers of ageing, life span and spontaneous tumour incidence in female Swiss-derived SHR mice. Biogerontology, 4(4), 193–202. https://pubmed.ncbi.nlm.nih.gov/14501183/
3. Khavinson, V., Linkova, N., Kvetnoy, I., & Kvetnaia, T. (2020). AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism. Molecules, 25(3), 609. https://pubmed.ncbi.nlm.nih.gov/32028714/
4. Al-dulaimi, S., Thomas, R., Matta, S., & Roberts, T. (2025). Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology, 26(5). https://pubmed.ncbi.nlm.nih.gov/40268845/ 

Disclaimer

Epithalon (Epitalon) is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition.

The Food and Drug Administration has not evaluated the statements on our website. This product is not approved for human or veterinary use. Researchers must comply with all applicable local, state, and federal laws and regulations governing the purchase and use of research compounds. By purchasing, you agree to our Terms and Conditions. RCDbio reserves the right to refuse sales to unauthorized individuals.

ATTENTION: All RCDbio products are strictly for LABORATORY AND RESEARCH PURPOSES ONLY. They are not intended for human consumption, veterinary use, or any other non-research application. For queries, complaints, or support, contact support@rcdbio.co