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What is Epithalon?
Epithalon (also spelled Epitalon) is a synthetic tetrapeptide with the amino acid sequence Ala-Glu-Asp-Gly, abbreviated AEDG. Molecular formula C14H22N4O9, molecular weight 390.3 Da, CAS 307297-39-8. Four residues makes it one of the smallest peptides in research circulation — smaller than GHK-Cu, and roughly a twelfth the mass of TB-500.
It did not start life as a designed molecule. Epithalon is the synthetic distillate of epithalamin, a crude polypeptide extract prepared from bovine pineal gland and studied from the late 1970s onward by Vladimir Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology. The working hypothesis was that the pineal gland releases short regulatory peptides that influence the pace of aging; AEDG was identified as the fragment carrying the activity, and synthesizing it removed the batch-to-batch variability that makes any tissue extract difficult to study.
Here is the part most vendor pages leave out. Nearly the entire telomerase literature on Epithalon originates from that same St. Petersburg group, and independent replication outside it is thin. The in-vitro finding that AEDG induces hTERT expression in human somatic cells is interesting and reasonably consistent within its source, but a mechanism supported largely by one laboratory over several decades sits in a different evidentiary category than one replicated across competing groups. Researchers designing around Epithalon should treat the telomerase story as a hypothesis worth testing rather than settled biology.
How Does Epithalon Work? Mechanism of Action
The mechanism most often attributed to Epithalon is upregulation of hTERT — human telomerase reverse transcriptase, the catalytic protein subunit of the telomerase holoenzyme. Telomerase extends chromosome ends by adding TTAGGG hexanucleotide repeats, offsetting the progressive telomere attrition that occurs each time a somatic cell divides. Cells that exhaust their telomere reserve stop dividing, which is the replicative limit Hayflick described in 1961. In cultured human somatic cells, AEDG exposure has been associated with recovered telomerase activity and delayed onset of replicative senescence.
How a four-residue peptide produces that effect is unresolved. No receptor for AEDG has been identified. The proposal advanced by the Khavinson group is direct interaction with DNA — that short peptides of this class bind specific promoter sequences and modulate transcription, a model sometimes described as peptide-gene regulation. It is a testable idea, and molecular docking work has been published in support of it, but there is no crystallographic or ChIP-level evidence that would make it conventional. Anyone citing a mechanism for Epithalon should say which model they are citing.
The pineal arm of the research is older than the telomerase arm and, in some respects, better grounded. Epithalon was developed as a pineal-regulating peptide, and studies report effects on melatonin synthesis and on expression of circadian clock genes including BMAL1, CLOCK and PER. Antioxidant enzyme upregulation appears in the same literature. Whether the circadian and telomere effects are two readouts of a single upstream event or two unrelated observations has not been demonstrated either way, though melatonin itself has independent published effects on telomere maintenance in cell models, which makes a link plausible.
The pharmacokinetic question is the one that most often goes unasked. AEDG is small, highly polar, carries two acidic side chains, and has no protecting modification at either terminus. Plasma peptidases clear molecules like this in minutes. For the nuclear transcription model to operate in an intact organism, an intact tetrapeptide has to reach a nucleus — and no published pharmacokinetic study establishes that it does. In-vitro work sidesteps the problem by applying the peptide directly to the culture medium, which is worth remembering when reading across from a cell result to a whole-animal claim.
Research Applications of Epithalon
Telomere and Telomerase Research
- hTERT expression assays: quantitative PCR for hTERT transcript level in treated somatic cell lines is the direct mechanistic readout, and the one the original claims rest on.
- TRAP (telomeric repeat amplification protocol) activity measurement: enzymatic telomerase activity, which is a separate question from transcript abundance and does not always track it.
- Replicative lifespan studies: population doubling counts in human fibroblast cultures carried to senescence, with telomere restriction fragment length as the structural endpoint.
Circadian and Pineal Signalling Models
- Clock gene expression panels: BMAL1, CLOCK and PER transcript profiling in pinealocyte and peripheral tissue models.
- Melatonin synthesis endpoints: AANAT and ASMT enzyme activity, which sit upstream of melatonin output and give a cleaner readout than melatonin concentration alone.
- Age-associated rhythm flattening: comparing amplitude of circadian gene oscillation between young and aged animal tissue is the standard preparation in the pineal-peptide literature.
Cellular Senescence and Oxidative Stress Models
- Senescence-associated beta-galactosidase staining: the conventional cytochemical marker for cells that have exited the cycle.
- Antioxidant enzyme activity: superoxide dismutase and catalase levels in aged cell preparations, reported alongside lipid peroxidation products.
- Comparative peptide screens: AEDG is frequently run against other short regulatory peptides from the same research programme, which is useful for ranking activity but does not substitute for an independent replication.
Epithalon vs Epithalamin
| Feature | Epithalon (Epitalon) | Epithalamin |
|---|---|---|
| Identity | Synthetic tetrapeptide, Ala-Glu-Asp-Gly | Crude polypeptide extract of bovine pineal gland |
| Composition | Single defined molecule | Mixture of peptides of varying length |
| Molecular weight | 390.3 Da | Not definable — heterogeneous mixture |
| Molecular formula | C14H22N4O9 | Not applicable |
| CAS number | 307297-39-8 | None assigned |
| Source | Solid-phase peptide synthesis | Animal tissue extraction |
| Batch reproducibility | High — verified by HPLC and LC-MS/MS | Low — composition varies with source tissue |
| Bovine material risk | None (fully synthetic) | Present — animal-derived preparation |
| Which came first | Derived from the extract in the 1980s | Studied from the late 1970s |
| Current research availability | Widely available as a research compound | Effectively unavailable outside historical literature |
Epithalon exists because epithalamin was impossible to study rigorously. You cannot attribute an effect to a molecule when your preparation is a tissue extract of unknown composition. Isolating AEDG and synthesizing it gave the research programme a defined molecule with a molecular weight, a CAS number and a reproducible batch — which is exactly why older epithalamin findings cannot be read directly onto Epithalon without re-testing.
Epithalon Technical Specifications
| Compound Name | Epithalon (Epitalon) |
|---|---|
| Common Synonyms | Epitalon, Epithalone, AEDG peptide, Ala-Glu-Asp-Gly tetrapeptide |
| IUPAC Name | L-Alanyl-L-alpha-glutamyl-L-alpha-aspartyl-glycine |
| Amino Acid Sequence | Ala-Glu-Asp-Gly (AEDG) |
| Amino Acid Count | 4 (tetrapeptide) |
| CAS Number | 307297-39-8 |
| Molecular Formula | C14H22N4O9 |
| Molecular Weight | 390.3 Da |
| Parent Preparation | Epithalamin (bovine pineal polypeptide extract) |
| Research Target | hTERT expression, telomerase activity, circadian clock genes |
| Purity | ≥99% by HPLC |
| Purity Confirmation | LC-MS/MS molecular weight verification |
| Endotoxin Testing | LAL (Limulus Amebocyte Lysate) method |
| Physical Form | Lyophilized powder |
| Appearance | White to off-white powder |
| Reconstitution | Bacteriostatic water or sterile 0.9% sodium chloride |
| Storage (lyophilized) | -20°C, desiccated, protected from light |
| Storage (reconstituted) | 2–8°C, use within 14–28 days |
| Shelf Life | 24 months from manufacture (lyophilized) |
| Testing Methods | HPLC, LC-MS/MS, LAL Endotoxin |
| Documentation | Certificate of Analysis (CoA) per batch |
| FDA Status | Not approved for human use; not a scheduled substance |
| Intended Use | In-vitro laboratory research only |
How to Reconstitute Epithalon for Research
Epithalon vials are usually small in mass — 10 mg is a common size — and the lyophilized cake can be almost invisible against the bottom of the vial. Do not assume an empty-looking vial is a short-fill. Add the diluent and watch the cake go; at 390.3 Da this peptide dissolves fast, often before you finish swirling.
- Bring the vial to room temperature before opening. Condensation on cold glass is the most common source of contamination at this step.
- Draw the calculated volume of bacteriostatic water. For a 10 mg vial, 2 mL yields 5 mg/mL; for the 50 mg vial, 5 mL yields 10 mg/mL.
- Swab the septum with 70% isopropyl alcohol and give it 30 seconds to dry. Wet alcohol carried into the vial on the needle is not sterilising anything.
- Angle the needle and run the diluent slowly down the inner wall rather than firing it into the cake. Foaming denatures peptide at the air-liquid interface.
- Swirl gently. AEDG goes into solution quickly — if anything is still visible after 60 seconds, keep swirling rather than shaking.
- Check that the solution is clear and colorless. Any cloudiness, discoloration or visible particulate means discard.
- Label with the reconstitution date and the resulting concentration in mg/mL.
- Store at 2–8°C and use within 14–28 days. Do not freeze the reconstituted solution or subject it to repeated thaw cycles.
Regulatory status: Epithalon is not approved by the FDA for any indication and is not a scheduled substance in the United States. Because it holds no approval from any governmental health authority, it falls within the scope of WADA Prohibited List section S0, which covers pharmacological substances without current regulatory approval. Sold by Peptide.Express for in-vitro laboratory research use only.
Research References
- Khavinson VK and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology produced the majority of the Epithalon telomerase literature. This search returns that corpus — it is presented as a search rather than a single citation because no one review is canonical, and because the concentration of the work in one group is itself a finding a researcher should see. Search PubMed for the Khavinson Epithalon telomerase corpus
- AEDG tetrapeptide gene-expression and peptide-DNA interaction literature, covering the proposed transcriptional regulation model and the circadian clock gene work. Search PubMed for AEDG peptide gene expression studies
- FDA drug approvals and databases — the authoritative record of approved drug products in the United States. Epithalon does not appear in it, which is the primary source behind the regulatory statement on this page. Search the FDA drug approval databases
All products are sold for in-vitro laboratory research use only. Not intended for human consumption, clinical use, or veterinary use.
Product Information
All products are third-party tested with 99%+ verified purity. Products are intended for in-vitro laboratory research use only. Not for human consumption.