Epithalon
Longevity & Cellular HealthPreclinicalAlso known as: Epitalon
Epithalon (also spelled Epitalon, sequence Ala-Glu-Asp-Gly / AEDG) is a synthetic tetrapeptide designed by Prof. Vladimir Khavinson at the St.
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Pre-filled · 10mg vial · 5000mcg dose
Overview
At A Glance
Epithalon's mechanism is best understood as pineal peptide mimesis, operating through three parallel pathways:…
Mechanism of Action
Epithalon's mechanism is best understood as pineal peptide mimesis, operating through three parallel pathways:
1. Telomerase activation and telomere elongation
The landmark finding is that 10 ng/mL AEDG in human fetal fibroblast cultures increased hTERT mRNA expression and activated telomerase, extending the Hayflick limit from ~34 population doublings to ~44 (Khavinson et al., 2003, Bull Exp Biol Med; Khavinson & Morozov, 2003). Subsequent studies confirmed telomere length increase of 33% in senescent human fibroblasts over 10 days of AEDG exposure (Khavinson, 2004).
Mechanistically, AEDG does not encode telomerase directly — it modulates chromatin at the hTERT promoter, de-repressing the gene in cells where it is normally silenced in adulthood. This is the single most-cited "anti-aging" finding for the peptide.
2. Melatonin restoration via pineal stimulation
Epithalon was derived from epithalamin, a crude bovine pineal extract used in Soviet geriatric medicine since the 1970s. The tetrapeptide preserves the active fragment responsible for stimulating pineal melatonin synthesis. In aged rats, a 10-day subcutaneous course restored the nocturnal melatonin rhythm to youthful amplitude (Anisimov et al., 2003). In humans (elderly cohort), similar protocols improved actigraphy-measured sleep efficiency and increased 6-sulfatoxymelatonin excretion by ~35% (Korkushko et al., 2011, Bull Exp Biol Med).
This is why users consistently report deeper, more restorative sleep as the earliest subjective effect — it is the most reliable signal across the dataset.
3. Direct DNA-binding epigenetic modulation
NMR spectroscopy and molecular docking studies show that AEDG binds the ACATAC and ATTTC motifs in double-stranded DNA via its glutamate-aspartate diad (Fedoreyeva et al., 2011, Biochemistry (Mosc)). This selective promoter binding alters transcription of:
- hTERT (telomerase catalytic subunit) — upregulated
- Interferon-γ — upregulated
- Matrix metalloproteinases — downregulated
- Cell-cycle inhibitors p16INK4a and p21 — modulated context-dependently
4. Antioxidant and anti-tumor adjunct effects (rodent)
Anisimov's group documented that chronic epithalon dosing in female mice reduced spontaneous tumor incidence from ~44% to ~23% over the life-span, and extended mean life-span by ~30% in CBA/Sto strain mice (Anisimov et al., 2003, Exp Gerontol; Anisimov et al., 2001). The mechanism is presumed to be a combination of immunomodulation (restored NK activity, T-cell rejuvenation) and reduced oxidative stress from circadian normalization.
5. Circadian gene expression in peripheral clocks
More recent work shows AEDG modulates expression of Bmal1, Per1/2, Clock, and Cry1/2 in peripheral tissues, restoring circadian amplitude in aged cells (Khavinson et al., 2020, Adv Gerontol). This is the molecular-level explanation for the subjective "I sleep like I did in my 30s" reports that characterize the peptide.
What epithalon does NOT do
- It does not cross the blood-brain barrier in large quantities; effects on sleep are thought to be mediated via peripheral pineal / suprachiasmatic signaling rather than direct CNS action.
- It is not a growth-hormone secretagogue (compare with CJC-1295/Ipamorelin).
- It does not raise IGF-1 or promote muscle accretion at therapeutic doses.
- It does not protect against DNA damage directly — its telomerase effect is promoter-mediated, not enzymatic rescue.
Overview
Epithalon (also spelled Epitalon, sequence Ala-Glu-Asp-Gly / AEDG) is a synthetic tetrapeptide designed by Prof. Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology in the 1980s as a short-chain analog of epithalamin, a peptide extract of bovine pineal gland. It is the most-studied "longevity peptide" in the Russian peer-reviewed literature, with over 30 years of published work on telomerase activation, telomere lengthening, melatonin restoration, and life-span extension in rodents.
The core biology is three-fold:
- Telomerase activation in somatic cells — Khavinson and Smirnova showed that 10 ng/mL AEDG increased hTERT expression and telomerase activity in human somatic fibroblasts, extending proliferative capacity by ~42% over the Hayflick limit (Khavinson et al., 2003, Bull Exp Biol Med).
- Restoration of pineal melatonin secretion — In aged rats and in elderly humans, epithalon restored the nocturnal melatonin peak that declines with pineal calcification, improving circadian amplitude and sleep architecture (Anisimov et al., 2003).
- Direct chromatin binding (epigenetic) — NMR and X-ray studies demonstrate that AEDG binds the major groove of DNA at specific sequences, modulating transcription of interferon-γ, hTERT, and cell-cycle regulators (Fedoreyeva et al., 2011).
Critical evidence-quality caveat: Unlike BPC-157 or the GLP-1 agonists, the human clinical evidence for Epithalon is almost entirely from Russian-language publications from a single research consortium (Khavinson / Anisimov / Korkushko). Western replication is minimal. The rodent data are compelling — a ~30% median life-span extension in female mice (Anisimov et al., 2003) — but translating this to human longevity remains hypothesis rather than demonstrated fact.
Epithalon is used in biohacking communities for:
- Sleep consolidation in adults over 40 (melatonin restoration)
- Telomere preservation as part of a longevity stack
- Circadian rhythm repair after shift-work or jet lag
- Adjunct in age-related immunosenescence
It is delivered by subcutaneous injection, typically 5-10 mg/day for 10-20 consecutive days, followed by a 3-6 month washout. This intermittent pulsing is intentional — Khavinson's protocols were always short-cycle, never continuous — and is a key safety feature in the absence of long-term continuous-dosing data.
Potential Research Fields
Chemical Information
IUPAC Name
L-alanyl-L-alpha-glutamyl-L-alpha-aspartylglycine
CAS Number
307297-39-8
Molecular Formula
C14H22N4O9
Molecular Mass
390.35 g/mol
Dosing & Protocols
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Interactions
Interaction Matrix
Contraindications
Absolute contraindications
- Active malignancy (any type) — hTERT upregulation is a theoretical pro-tumorigenic signal; avoid until complete remission with clinical clearance.
- History of hormone-sensitive cancer (breast, prostate, endometrial) within 5 years — insufficient data to stratify risk; conservative approach is avoidance.
- Pregnancy and lactation — no safety data.
- Active immunosuppression (transplant medication, biologics) — unknown interaction with interferon-γ upregulation.
- Active untreated autoimmune disease (lupus, rheumatoid arthritis, MS in flare) — theoretical risk of disease flare via Th1 potentiation; avoid until stable and discussed with rheumatologist.
Relative contraindications
- Remote hormone-sensitive cancer (>5 years remission) — discuss with oncologist; consider risk/benefit individually.
- Psychiatric disorders with sleep-rhythm sensitivity (bipolar, cyclothymia) — melatonin amplification may destabilize mood cycles in rare cases.
- Chronic kidney disease stage 4-5 — limited data on peptide clearance; use cautiously if at all.
- Hemophilia or active anticoagulation — injection-site bleeding risk; use SC not IM, rotate sites.
Drug interactions to be aware of
- Exogenous melatonin — not a true interaction but additive sleep pressure; reduce melatonin dose 50% during epithalon cycles.
- SSRIs / SNRIs — no pharmacokinetic interaction, but increased dream vividness may be bothersome.
- Immunosuppressants — avoid or use under specialist supervision.
- Chemotherapy / radiation therapy — concurrent use has no evidence base; avoid.
Surgery and procedure considerations
- Hold for 2 weeks pre-elective surgery (conservative; no actual bleeding concern demonstrated).
- No pulse-oximetry interference (distinguishes from methylene blue).
- Disclose use to all clinicians.
What to disclose to any clinician
- Dose, frequency, brand/vendor, COA availability
- Cycle dates and duration
- All concurrent supplements and peptides
- Prior peptide history (lifetime exposure estimate)
Research Disclaimer
This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds.
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| Vendor | Product | Form | Qty | Price | $/mg | Coupon | |
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Epithalon 10mg | vial | 1 vial● In Stock | $35.00BEST | $3.500 | — | |
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Epithalon 50mg | vial | 1 vial● Out of Stock | $119.00VALUE | $2.380 | — | Sign in for stock alert |
| Forever Young Spray | spray | 0mg● In Stock | $60.00 | — | |||
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Epithalon 10mg | vial | 1 vial● In Stock | $34.99 | $3.499 | ||
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Epithalon 10mg | vial | 10mg vial● In Stock | $34.99 | $3.499 |
Tracking since Apr 6, 2026 · 4 data points
Price History
3 data pointsVendors Selling Epithalon
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Ion Peptide
Adera
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Quick Facts
Half-Life
~4 hours (estimated from peptide pharmacokinetic modeling; functional gene expression effects persist 24+ hours)
Molecular Weight
390.35 g/mol
Administration
Subcutaneous
CAS Number
307297-39-8
Trial Phase
Preclinical
Safety Profile
Common Side Effects
- • Injection site redness or mild irritation (subcutaneous administration)
- • Mild drowsiness during evening administration (likely due to melatonin stimulation)
- • Transient flushing reported anecdotally
Research Disclaimer
This information is for educational and research purposes only. Not intended as medical advice. Consult a healthcare professional before use.
Frequently Asked Questions
How strong is the human evidence for epithalon's longevity claims?
The rodent data is strong (~30% median life-span extension across multiple mouse strains, reproduced over 20 years by the Anisimov/Khavinson consortium). The human data is suggestive but almost entirely from Russian-language publications, with the Korkushko 2011 elderly cohort study being the most-cited — 39 patients over 6 years with annual 10-day cycles, showing ~2.5x lower mortality. No Western double-blind RCT exists. Treat epithalon as plausible-but-unproven for human longevity endpoints, and well-evidenced for short-term sleep and melatonin restoration in older adults.
Will I notice anything during my first cycle?
The most reliable subjective effect is deeper, more consolidated sleep starting around night 3-5 of a cycle. Many users report more vivid dreams in the first week (consistent with restored REM pressure from melatonin rise). Energy and mood improvements in the day typically lag sleep changes by a week or so. If you are under 40 with already-good sleep, the effect may be subtle. If you are over 50 with age-related sleep fragmentation, the effect is usually obvious by the end of week 2.
How often should I cycle epithalon?
Standard Khavinson protocol: 10-20 consecutive days, then minimum 3 months off. Most biohackers run 1-2 cycles per year separated by 6 months. The Korkushko 6-year elderly cohort used annual 10-day cycles. Continuous daily dosing is NOT evidenced and is contrary to every published protocol. The pulsing pattern is thought to be functionally important — it allows the pineal axis to re-regulate rather than downregulating in response to sustained stimulation.
Is epithalon safe for someone with a history of cancer?
It is an absolute contraindication during active malignancy and a relative contraindication for at least 5 years after hormone-sensitive cancer (breast, prostate, endometrial). The mechanism — hTERT upregulation via promoter demethylation — is theoretically pro-tumorigenic, even though rodent data paradoxically show reduced tumor incidence (possibly via immune rejuvenation). Without human data to stratify this risk, the conservative approach is to avoid. Survivors of long-remission non-hormone-sensitive cancers should discuss individually with an oncologist.
Can I take epithalon orally instead of injection?
Oral bioavailability is essentially zero. AEDG is a short peptide rapidly hydrolyzed by gastric and intestinal proteases. Sublingual formulations exist in some vendor catalogs but lack published bioavailability data and no human trial has used them. All published clinical and preclinical protocols use subcutaneous or intramuscular injection. If you cannot or will not inject, epithalon is not a practical option for you — this is a peptide where delivery matters.
What is the difference between epithalon and epithalamin?
Epithalamin is the crude bovine pineal extract used in Soviet/Russian geriatric medicine from the 1970s onward — a mixture of many pineal peptides. Epithalon (AEDG) is the synthetic four-amino-acid tetrapeptide that Khavinson identified as the active fragment. Epithalon is purer, more consistent, and easier to dose; epithalamin is rarely used today outside specific Russian clinical contexts. When biohackers say 'epithalon,' they almost always mean the synthetic tetrapeptide.
Can I stack epithalon with other peptides like BPC-157 or CJC-1295?
Yes, with two caveats. First, isolate variables in your first epithalon cycle — you want to know what epithalon does to your sleep before introducing another variable. Second, combining with a GH secretagogue (CJC-1295, ipamorelin) or healing peptide (BPC-157) has no documented pharmacologic interaction but lacks controlled safety data in combination. Most users run epithalon as a twice-yearly standalone cycle and use other peptides continuously in the intervening months. See our Peptide Stacking Guide for structured combinations.
Do I need a telomere length test to benefit from epithalon?
No. Telomere length assays (Life Length, Telomere Diagnostics, SpectraCell) have significant methodological variability — same-day duplicate samples can differ 10-20% — and no clinical guideline supports using them to make peptide decisions. If you want to track telomere length for curiosity or longitudinal self-quantification, do it consistently with the same lab and same assay; expect noisy data. The best proximate biomarker for whether epithalon is working for you is objective sleep data (deep sleep minutes, HRV, sleep efficiency) from an Oura or Whoop.
Why is epithalon not FDA-approved if the data is so strong in Russia?
Three reasons. First, the bulk of the human data is in Russian-language journals not indexed in Western regulatory databases, and translation quality and study methodology vary. Second, there has been no pharmaceutical sponsor willing to fund a registrational-quality Phase 3 program — the molecule is off-patent and commercial incentive is limited. Third, longevity endpoints are inherently long-duration and expensive to test. The result is a peptide with 30+ years of research use in Russia but research-only status in the US and EU. This is why vendor-grade material should always be sourced with a valid COA and handled as a research chemical.
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