Epithalon
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Research Use Only
These products are for laboratory research only and not intended for medical use. They are not FDA-approved to diagnose, treat, cure, or prevent any disease. By purchasing, you certify they will be used solely for research and not for human or animal consumption.
Research Summary
Research Overview Epithalon (Ala-Glu-Asp-Gly) is a synthetic tetrapeptide geroprotector developed by Prof. Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology as the active component of Epithalamin (bovine pineal gland extract). Its discovery originated from 1970s Soviet military research to protect soldiers from radiation and accelerated aging.[4] Epithalon's mechanism is fundamentally different from classical receptor-ligand pharmacology. Rather than binding a cell surface receptor, it enters the nucleus and interacts directly with DNA (targeting CAG repeats and ATTTC promoter sequences) and histone proteins (H1.3, H1.6) — functioning as an epigenetic switch that converts heterochromatin to euchromatin, making silenced genes accessible for transcription.[1][3] Research spans 10+ indication categories across gerontology, oncology, ophthalmology, endocrinology, and neuroscience — with over 50 years of study (1970s–2025). The "Epithalon Paradox" — activating telomerase while simultaneously inhibiting cancer — challenges conventional oncological assumptions and remains a major focus of current research.[7]
Epithalon — Research Data at a Glance
| Property | Value |
|---|---|
| Contributing Researchers | 3 |
| Purity Standard | ≥99% (HPLC verified, 3rd-party COA) |
| Research Use Only | Not for human consumption. RUO only. |
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Overview
Research Overview
Epithalon (Ala-Glu-Asp-Gly) is a synthetic tetrapeptide geroprotector developed by Prof. Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology as the active component of Epithalamin (bovine pineal gland extract). Its discovery originated from 1970s Soviet military research to protect soldiers from radiation and accelerated aging.[4]
Epithalon's mechanism is fundamentally different from classical receptor-ligand pharmacology. Rather than binding a cell surface receptor, it enters the nucleus and interacts directly with DNA (targeting CAG repeats and ATTTC promoter sequences) and histone proteins (H1.3, H1.6) — functioning as an epigenetic switch that converts heterochromatin to euchromatin, making silenced genes accessible for transcription.[1][3]
Research spans 10+ indication categories across gerontology, oncology, ophthalmology, endocrinology, and neuroscience — with over 50 years of study (1970s–2025). The "Epithalon Paradox" — activating telomerase while simultaneously inhibiting cancer — challenges conventional oncological assumptions and remains a major focus of current research.[7]
Mechanism of Action
Mechanism of Action
Epithalon operates via a receptor-independent, epigenetic mechanism — bypassing cell surface receptors to directly interact with the genome. It penetrates the cell nucleus and binds to DNA and histone proteins, functioning as a master gene regulator.[3][1]
Primary Epigenetic Targets
| Target | Mechanism | Downstream Effect |
|---|---|---|
| DNA — CAG repeats & ATTTC sequences | Binds major groove of DNA double helix | Lowers chromatin melting temperature → prevents genomic "hardening" with age |
| Histone H1.3 & H1.6 | High-affinity binding → decondenses heterochromatin → euchromatin | Silenced genes become accessible for transcription |
| hTERT gene promoter | Direct promoter binding → upregulates hTERT mRNA (12-fold at 1 µg/mL) | Telomerase synthesis → TTAGGG repeat elongation |
Dual Telomere Mechanism (Al-dulaimi et al., 2025)
| Cell Type | Mechanism | Markers |
|---|---|---|
| Normal somatic cells | Telomerase-mediated elongation (classic pathway) | ↑ hTERT mRNA → ↑ telomerase activity → TTAGGG addition |
| Cancer cells | ALT (Alternative Lengthening of Telomeres) via replication stress | C-circles, PML bodies — NOT increased telomerase activity |
Downstream Signaling Cascades
| Pathway | Targets | Effect |
|---|---|---|
| Melatonin Synthesis | ↑ AANAT + pCREB in pinealocytes | Restores nighttime melatonin production |
| Antioxidant Defense | Keap1/Nrf2 pathway activation | ↑ SOD, Catalase, Glutathione Peroxidase |
| Immune Signaling | ↑ STAT1 + ERK1/2 phosphorylation; ↑ IL-2 mRNA (within 5h) | T-cell proliferation; NO STAT3 activation |
| Circadian Clock | Modulates Clock, Cry2, Csnk1e genes | Restores youthful circadian rhythms |
No opioid receptor binding — Epithalon does not interact with µ or δ opioid receptors despite being a peptide. Its STAT1 phosphorylation is believed to be receptor-independent.[3]
Research Applications
Research Applications
Epithalon research spans 10+ indication categories with over 50 years of investigation (1970s–2025):
- Telomere Extension & Cellular Senescence — Cells surpass Hayflick limit; telomere elongation confirmed in patients aged 60–80 (9.61→10.72 kb and 7.51→8.91 kb, p<0.05).[5]
- Cancer Prevention Paradox — Inhibits spontaneous tumors in HER-2/neu mice; reduces oncogene expression 3.7-fold; anti-metastatic — despite telomerase activation.[7][14]
- Retinal Degeneration / Retinitis Pigmentosa — 90% positive clinical effect in 162 patients; visual field expanded 90–120°.[9]
- Circadian Rhythm & Sleep Regulation — Restores youthful melatonin secretion; normalizes cortisol rhythms in aged monkeys and humans.[11][15]
- Neuroprotection & Neurogenesis — Upregulates Nestin, GAP43, Beta-Tubulin III in stem cells; promotes neuronal differentiation.[3]
- Immune System Rejuvenation — ↑ IL-2, T-cell proliferation; corrects age-related CD4+/CD8+ ratios.[4]
- Antioxidant Defense — ↑ SOD (+41%), catalase (+20%), glutathione peroxidase; ↓ lipid peroxidation and ROS.[6]
- Diabetic Retinopathy / Wound Healing — Inhibits EMT and fibrosis in high-glucose RPE cells.[12]
- Reproductive Health — Restores estrous cycles in aged rats; improves oocyte quality and blastocyst hatching.[10]
- Geroprotection / Anti-Aging — Maximum lifespan increased 12–13% in mice; up to 24% in CBA model; reduced chromosomal aberrations.[7][8]
Biochemical Characteristics
| Property | Value |
|---|---|
| Molecular Formula | C₁₄H₂₂N₄O₉ |
| Molecular Weight | 390.35 Da |
| CAS Number | 307297-39-8 |
| PubChem CID | 219042 |
| Sequence (1-Letter) | AEDG |
| Sequence (3-Letter) | Ala-Glu-Asp-Gly |
| Structure | Linear tetrapeptide; four L-amino acids; no disulfide bridges |
| InChI Key | HGHOBRRUMWJWCU-FXQIFTODSA-N |
| Origin | Synthetic analog of Epithalamin (bovine pineal gland extract) |
| Classification | Peptide Bioregulator / Geroprotector / Research Peptide |
| Dose-Response | Bell-shaped / non-linear — peak activity at ultra-low concentrations (10⁻¹⁷ to 10⁻¹⁵ M) |
Identifiers
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Preclinical Research Summary
Preclinical Research Summary
Key Preclinical Studies
| Study | Model | Key Findings | Ref |
|---|---|---|---|
| Anisimov/Popovich et al. (2003) | SHR mice — 1 µg/mouse SC × 5d/month from 3 mo | Last 10% lifespan increased 13.3%; chromosomal aberrations ↓17.1%; leukemia inhibited 6-fold | [7] |
| Anisimov et al. (2002) | HER-2/neu transgenic mice — 1 µg/mouse SC monthly | HER-2/neu mRNA reduced 3.7-fold; breast adenocarcinoma incidence significantly reduced | [14] |
| Kossoy et al. (2006) | C3H/He mice — 0.1 µg/mouse SC × 5x/wk × 6.5 mo | Reduced tumor metastasis and multiplicity | [8] |
| Anisimov et al. (2001) | CBA mice — 0.1 µg/mouse SC monthly | Oldest treated mouse lived 34 months vs 24 mo control; mice reaching 23 mo increased 4-fold | [8] |
| Khavinson et al. (2002–03) | Campbell rats — 1 µg/rat parabulbar injection | Retinal function prolonged 43.9%; 90% of retinal layers preserved at day 41 vs complete destruction | [9] |
| Zamorskii et al. (2014–19) | Rats with acute kidney failure — 7 µg/kg IM/IP × 7–10d | Nephroprotective — increased diuresis, decreased proteinuria, ↑ catalase and glutathione peroxidase | [13] |
| Goncharova et al. (2001–05) | Old female rhesus monkeys — 10 µg/kg IM | Restored nighttime melatonin synthesis; normalized cortisol circadian rhythm; improved glucose tolerance | [11] |
| Khavinson et al. (2000–01) | Drosophila — 0.00001–0.001% in medium | Mean lifespan +11–16%, max +14%; mortality ↓52%; SOD +41%, catalase +20% | [6] |
| Ullah et al. (2025) | Bovine oocytes in vitro | Activated telomerase; improved blastocyst hatching; reduced ROS | [10] |
Clinical / Human Studies
| Trial | Population | Intervention | Key Results | Ref |
|---|---|---|---|---|
| Retinitis Pigmentosa | n=162 patients | 5.0 µg parabulbar daily × 10 days | 90% positive effect; visual acuity +0.15–0.20; visual field expanded 90–120° in 64.8% | [9] |
| Circadian Rhythm | n=75 women, age 60–74 | 0.5 mg sublingual daily × 20 days | Melatonin +1.6-fold; Clock ↓1.8×, Cry2 ↑2×, Csnk1e ↓2.1× | [15] |
| Telomere Elongation | Patients aged 60–80 | Standard protocol | Ages 60–65: 9.61→10.72 kb; Ages 75–80: 7.51→8.91 kb (both p<0.05) | [5] |
| Pulmonary Tuberculosis | TB patients | Not specified | Protective effect against further chromosomal aberrations (mixed outcome) | [16] |
Safety Summary
| Parameter | Finding |
|---|---|
| Long-term Animal Studies | No toxicity in mice/rats from 3 months of age until natural death; reduced mortality and spontaneous tumors |
| Clinical Trials | No severe adverse events in retinitis pigmentosa (n=162) or circadian rhythm trials; mild injection site reactions reported anecdotally |
| Cancer Risk Paradox | Despite telomerase activation, animal studies consistently show ANTI-tumor and anti-metastatic effects |
| Degradation | N-terminal glutamic acid can cyclize to pyroglutamate; TFA salt affects net peptide content |
| Routes Studied | Subcutaneous, intramuscular, parabulbar (eye), sublingual, oral, intranasal |
Authors & Attribution
✍️ Article Author
Prof. Vladimir Khavinson, M.D., Ph.D.
Prof. Vladimir Khavinson is the Director of the St. Petersburg Institute of Bioregulation and Gerontology, a Member of the Russian Academy of Sciences, and a retired Colonel of Medical Service. He is the primary inventor and pioneer of peptide bioregulators, leading the original discovery of Epithalamin (pineal gland extract) and the subsequent synthesis of Epithalon (Ala-Glu-Asp-Gly). His research established the 'peptide theory of aging,' demonstrating Epithalon's ability to reactivate telomerase, elongate telomeres, and regulate gene expression at the epigenetic level. Foundational research began in the 1970s at the S.M. Kirov Military Medical Academy in the Soviet Union. Key publications include 'Epithalon Peptide Induces Telomerase Activity and Telomere Elongation in Human Somatic Cells' (2003) and 'AEDG Peptide Stimulates Gene Expression during Neurogenesis' (2020). Prof. Vladimir Khavinson is referenced as the leading scientist in Epithalon research. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →🎓 Scientific Journal Author
Prof. Vladimir N. Anisimov, M.D., Ph.D.
Prof. Vladimir N. Anisimov is a researcher at the N.N. Petrov Research Institute of Oncology (St. Petersburg, Russia). He has been instrumental in characterizing the geroprotective and oncostatic properties of Epithalon in animal models, providing decades of critical evidence that while Epithalon extends telomeres, it does not promote cancer — paradoxically inhibiting spontaneous tumor development and extending lifespan in mice. His work established the 'Epithalon Paradox' in gerontological research. Key publications include 'Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in SHR mice' (Biogerontology, 2003) and 'Inhibitory effect on HER-2/neu mammary tumors' (2002). Prof. Vladimir Anisimov is referenced as a leading scientist in Epithalon research. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →Prof. Vladimir N. Anisimov, M.D., Ph.D. is being referenced as one of the leading scientists involved in the research and development of Epithalon. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide.
🔬 Contributing Researcher
Prof. Natalia S. Linkova
Prof. Natalia S. Linkova is a Doctor of Biological Sciences at the St. Petersburg Institute of Bioregulation and Gerontology and the Academy of Postgraduate Education under FSBU FSCC of FMBA of Russia. She is a prominent researcher in the molecular mechanisms of peptide bioregulators, focusing on how Epithalon interacts with DNA and histone proteins to regulate gene expression, neurogenesis, and cell differentiation — providing the mechanistic explanation for the peptide's broad biological effects. Key publications include 'AEDG Peptide Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism' (Molecules, 2020) and 'Peptide Regulation of Gene Expression: A Systematic Review' (2021). Prof. Natalia Linkova is referenced as a leading scientist in Epithalon research. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →Prof. Natalia S. Linkova is being referenced as one of the leading scientists involved in the research and development of Epithalon. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide.
RUO Disclaimer
For Research Use Only (RUO). This product is intended solely for in-vitro research and laboratory experimentation. It is not a drug, food, cosmetic, or medical device and has not been approved by the FDA for any human or veterinary use. It must not be used for therapeutic, diagnostic, or any other non-research purpose. Pure US Peptide does not condone or encourage the use of this product for anything other than strictly defined research applications. Users assume full responsibility for compliance with all applicable regulations and guidelines.
Certificate of Analysis (COA)
Every batch is strictly tested by accredited third-party laboratories (ISO 17025) to ensure 99%+ purity.
Latest Lab Report
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