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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Overview
At A Glance
Epithalon (AEDG; Ala-Glu-Asp-Gly) is a synthetic tetrapeptide modeled on the pineal polypeptide preparation epithalamin. Its proposed mechanism spans several parallel pathways. The human-relevant evidence is strongest for melatonin/circadian effects; the strongest laboratory evid…
Mechanism of Action
Epithalon (AEDG; Ala-Glu-Asp-Gly) is a synthetic tetrapeptide modeled on the pineal polypeptide preparation epithalamin. Its proposed mechanism spans several parallel pathways. The human-relevant evidence is strongest for melatonin/circadian effects; the strongest laboratory evidence is the telomerase work in human cell culture.
1. Telomerase activation and telomere elongation (human cell culture)
The most-cited finding is that Epithalon added to telomerase-negative human fetal fibroblasts induced expression of the telomerase catalytic subunit (hTERT), restored telomerase activity, and elongated telomeres ([PMID:12937682] - Khavinson, Bondarev & Butyugov, Bull Exp Biol Med, 2003). In a follow-up, fibroblasts that normally senesced at passage 34 underwent roughly 10 additional divisions (to passage ~44), overcoming the Hayflick limit, with telomeres re-lengthened toward early-passage size ([PMID:15455129] - Khavinson et al., Bull Exp Biol Med, 2004). These are in-vitro results in cultured cells; the peptide is not itself a telomerase enzyme and appears to de-repress the hTERT gene rather than encode it. (The figure often quoted online - a 33% telomere increase at 10 ng/mL over 10 days - is not stated in the primary papers and should not be treated as established.)
2. Melatonin restoration via pineal signalling
Epithalon derives from epithalamin, a pineal peptide preparation used in Soviet/Russian geriatric medicine since the 1970s. In a randomized controlled trial in elderly coronary patients, courses of epithalamin normalized the circadian rhythm of melatonin production and of carbohydrate/lipid metabolism ([PMID:22451889] - Korkushko, Khavinson et al., Bull Exp Biol Med, 2011). This melatonin/circadian normalization is the most plausible basis for the deeper, more consolidated sleep users report as the earliest subjective effect. Note that the human melatonin data derive chiefly from epithalamin (the parent preparation), not from the isolated AEDG tetrapeptide.
3. Site-specific DNA / chromatin binding (proposed epigenetic modulation)
Fluorescence and nuclear-penetration studies show AEDG enters the cell nucleus and binds single- and double-stranded DNA and deoxyribooligonucleotides in a sequence-specific manner, discriminating cytosine-methylation status and binding preferentially to CNG- and CAG-containing sequences ([PMID:22117547] - Fedoreyeva et al., Biochemistry (Mosc), 2011). This site-specific binding is proposed as an epigenetic route by which short peptides could influence gene activity. (Earlier claims that AEDG specifically targets "ACATAC/ATTTC" promoter motifs are not supported by this work.)
4. Rodent life-span and tumor data - what it actually shows
The Anisimov/Khavinson group tested Epitalon in several mouse strains, and the real effects are modest. In outbred Swiss-derived SHR mice, Epitalon did not change mean life span; it increased the life span of the last 10% of survivors by ~13% and maximum life span by ~12%, reduced bone-marrow chromosome aberrations by ~17%, and did not change total spontaneous tumor incidence, though it suppressed leukemia roughly 6-fold ([PMID:14501183] - Anisimov et al., Biogerontology, 2003). In CBA mice, chronic dosing modestly prolonged life span with a reduction in spontaneous tumor incidence ([PMID:11227856] - Anisimov et al., Ross Fiziol Zh, 2001). In senescence-accelerated (SAM) mice it lengthened survival among the longest-lived animals without changing overall tumor frequency ([PMID:15909815] - Anisimov et al., Vopr Onkol, 2005). These are genuine but modest, tail-of-survival effects - not the "~30% life-span extension" or "tumor incidence 44%23%" figures that circulate in vendor copy.
What epithalon does NOT do
- It is not a growth-hormone secretagogue and does not raise IGF-1 or drive muscle accretion (contrast CJC-1295/Ipamorelin).
- It has no FDA- or EMA-approved indication, and Western human evidence is limited.
- Its telomerase effect is promoter-level de-repression in cell culture, not a demonstrated systemic anti-aging effect in humans.
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
Amino Acid Sequence
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.
$34.99
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| Vendor | Product | Form | Qty | Price | $/mg | Coupon | |
|---|---|---|---|---|---|---|---|
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Epithalon 10mg | vial | 1 vial● In Stock | $34.99BEST | $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
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Quick Facts
Half-Life
Not well characterized in humans. As a small tetrapeptide, AEDG is expected to have a very short plasma half-life (on the order of minutes), while downstream gene-expression and circadian effects are thought to persist considerably longer. Any specific half-life figure should be treated as an unvalidated estimate.
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 real but modest: across SHR, CBA and SAM mouse strains, Epitalon mainly extended maximum and late-survivor lifespan (roughly 10-13% in the last 10% of survivors) rather than mean lifespan, reduced certain tumors (about 6-fold fewer leukemias in SHR mice) without lowering total tumor incidence, and cut chromosome aberrations - it did not produce the ~30% lifespan jumps sometimes claimed online. The human data are almost entirely from one Russian/Ukrainian group and largely use epithalamin (the parent pineal preparation), not the isolated AEDG tetrapeptide; the most-cited is a randomized controlled study in elderly coronary patients (Korkushko/Khavinson 2011) reporting decelerated cardiovascular aging, normalized melatonin rhythm and significantly lower mortality. No Western double-blind RCT exists. Treat epithalon as plausible-but-unproven for human longevity endpoints, and at best suggestive for sleep and melatonin support 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 Russian protocol: 10-20 consecutive days, then a minimum of 3 months off. Most biohackers run 1-2 cycles per year separated by ~6 months. The most-cited elderly trial (Korkushko/Khavinson) actually used the parent preparation epithalamin as 6 courses over 3 years with long-term follow-up, not continuous dosing. Continuous daily dosing is not evidenced and is contrary to every published protocol; the pulsed pattern is thought to matter, letting the pineal axis re-regulate rather than downregulate under 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 incidence of certain tumors (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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