Epithalon molecular structure
Epithalon molecular structure
Experimental
Longevity

Epithalon

Also known as: Epitalon, Epithalone, AGAG Peptide, Ala-Glu-Asp-Gly, Epithalamin Synthetic Analog

MW

390.35 Da

Formula

C14H22N4O9

CAS

307297-39-8

Routes

3 routes

Epithalon (epitalon) is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) developed by Professor Vladimir Khavinson at the Saint Petersburg Institute of Bioregulation and Gerontology. It is the synthetic analog of epithalamin, a polypeptide extract from the pineal gland that demonstrated life-extending properties in animal studies beginning in the 1980s. Epithalon's primary mechanism centers on activation of telomerase — the enzyme that maintains and elongates telomeres, the protective caps on chromosome ends that shorten with each cell division. Telomere shortening is a fundamental mechanism of cellular aging, and epithalon's ability to reactivate telomerase in somatic cells has positioned it as one of the most studied peptides in longevity research. Beyond telomerase activation, epithalon normalizes circadian melatonin production from the pineal gland, acts as a powerful antioxidant, and has demonstrated life-extending effects of 12-24% in multiple animal species. While human clinical data remains limited, the peptide has accumulated over 35 years of preclinical and clinical research primarily from Russian biogerontology studies.

Research Use OnlyFor educational and research purposes only

Research Applications

Lifespan Extension

The most compelling research application of epithalon is longevity. Studies in mice, rats, Drosophila, and other organisms demonstrate 12-24% lifespan extension with chronic epithalon administration. These effects are attributed to telomere maintenance, reduced oxidative damage, and neuroendocrine optimization.

Telomere Biology Research

Epithalon is a valuable research tool for studying telomere dynamics in aging and disease. It enables investigation of telomerase reactivation in somatic cells without viral vectors or gene therapy, providing a pharmacological approach to telomere biology research.

Age-Related Disease Prevention

Preclinical studies show epithalon reduces incidence of spontaneous tumors in aging animals, delays age-related pathology in multiple organ systems, and improves survival in models of cardiovascular disease and neurodegeneration.

Circadian Rhythm Restoration

Research demonstrates epithalon normalizes age-disrupted circadian rhythms by restoring pineal melatonin synthesis. This has applications in age-related insomnia, jet lag, shift work disorders, and the broader disruption of circadian function in aging.

Retinal Protection

Studies show epithalon protects retinal pigment epithelium from degenerative changes, suggesting potential applications in age-related macular degeneration (AMD) and other retinopathies. The peptide maintains retinal cell viability and function through anti-apoptotic and antioxidant mechanisms.

Immune Function Restoration

Epithalon research demonstrates restoration of T-cell function and thymic output in aging, countering immunosenescence. It improves lymphocyte proliferative responses and cytokine production in aged subjects.

Mechanism of Action

Telomerase Activation

Epithalon activates the catalytic subunit of telomerase (hTERT) in somatic cells. Normally, hTERT expression is silenced in most adult cells, leading to progressive telomere shortening with each cell division (the Hayflick limit). Epithalon induces hTERT gene expression through chromatin remodeling at the hTERT promoter, enabling telomere elongation and extending cellular replicative capacity. Studies in human fibroblasts show epithalon extends passage number by 10-15 additional doublings.

Pineal Gland Melatonin Regulation

Epithalon acts on pinealocytes to restore youthful melatonin synthesis patterns. With aging, pineal calcification and reduced enzyme activity lead to diminished melatonin production. Epithalon upregulates the key melatonin synthesis enzymes — AANAT (arylalkylamine N-acetyltransferase) and HIOMT (hydroxyindole-O-methyltransferase) — restoring nocturnal melatonin peaks toward youthful levels.

Antioxidant Gene Expression

Epithalon upregulates endogenous antioxidant enzyme systems including superoxide dismutase (SOD), catalase, and glutathione peroxidase. This reduces oxidative damage to DNA, proteins, and lipids — a primary driver of aging at the cellular level.

Neuroendocrine Clock Regulation

Through pineal gland restoration, epithalon normalizes the aging neuroendocrine clock, improving circadian rhythm integrity, hypothalamic-pituitary axis function, and hormonal balance. This systemic neuroendocrine normalization contributes to the broad anti-aging effects observed in animal studies.

Cell Cycle and Apoptosis Regulation

Epithalon modulates cell cycle progression by regulating p53, p21, and Rb signaling. It maintains proper cell cycle checkpoints while extending replicative capacity — a critical distinction from oncogenic telomerase activation, as epithalon preserves normal tumor suppressor function.

Biological Pathways

hTERT/Telomerase Pathway

Epithalon induces hTERT transcription through activation of the hTERT promoter, involving Sp1 and c-Myc transcription factors. Reactivated telomerase adds TTAGGG repeats to chromosome ends, preventing telomere-mediated senescence and maintaining genomic stability in dividing cells.

Melatonin/Clock Gene Circuit

Restored melatonin production normalizes core clock gene expression (BMAL1, CLOCK, PER, CRY), improving circadian coordination of metabolic, immune, and endocrine functions. Melatonin itself acts as a potent antioxidant and immunomodulator, amplifying epithalon's direct effects.

Nrf2/ARE Antioxidant Pathway

Epithalon activates the Nrf2 transcription factor, driving expression of phase II detoxification and antioxidant genes through the Antioxidant Response Element (ARE). This includes upregulation of heme oxygenase-1, NAD(P)H quinone dehydrogenase, and glutathione S-transferase.

p53/p21 Cell Cycle Control

Epithalon maintains functional p53 signaling while preventing premature senescence. This balance allows cells to continue dividing with properly functioning DNA damage checkpoints — extending healthy lifespan without increasing cancer susceptibility.

Dosage Information

Typical dosage ranges for research applications. Always verify with current literature.
Typical Dose
7,500 mcg
Dose Range
5,000 - 10,000 mcg
Frequency
Daily for 10-20 consecutive days, 1-2x yearly
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Calculation Results

Concentration
2.5 mg/ml
Dose Volume
0.1 ml0.100 ml
Insulin Syringe
10 units
Doses per Vial
2020 doses @ 250 mcg

Syringe Fill Level (100u syringe)

05010010.0uunits
0u10.0 / 100 units (10%)100u

Protocols

Epithalon Telomere Repair Protocol
Advanced
Anti-Aging
15 days (50mg course)

Russian anti-aging peptide for telomerase activation and cellular rejuvenation.

Dosage
10mg every 3 days (5 doses = 50mg course)
Frequency
IM injection every 3 days
Cycle
Repeat courses every 6 months. 6 courses over 3 years recommended (300mg total).
Stacking Notes
Can combine with NAD+ precursors (NMN 500mg daily) for enhanced longevity effects.

Warning: Limited human studies. Based on Russian research.

Comprehensive Longevity Stack
Advanced
Anti-Aging
3-6 months

Multi-peptide anti-aging protocol combining telomerase activation, mitochondrial support, and GH optimization.

Dosage
Epithalon: 1mg daily, MOTS-c: 10mg 2x/week, NAD+: 500mg daily, CJC/Ipa: 200mcg each daily
Frequency
Daily or as specified per peptide
Cycle
Epithalon: 50-day course yearly. MOTS-c: Ongoing 2x/week. NAD+: Daily. CJC/Ipa: 5 on/2 off.
Stacking Notes
Comprehensive approach targeting multiple aging pathways. Requires significant commitment and cost.

Warning: Very advanced protocol. Consider blood work monitoring.

Stability & Storage

Epithalon is supplied as a white lyophilized powder. Store at -20°C for long-term stability (24+ months). At 2-8°C, stability is approximately 6-12 months. The tetrapeptide is relatively stable due to its small size and lack of oxidation-prone residues.

Reconstitute with bacteriostatic water or sterile water. The solution should be clear and colorless. Store reconstituted epithalon at 2-8°C and use within 21-28 days.

Epithalon is one of the more stable peptides due to its small size (4 amino acids, 390 Da) and absence of cysteine/methionine residues susceptible to oxidation. It can tolerate brief exposure to room temperature without significant degradation. Protect from prolonged UV light exposure.

Side Effects & Precautions

Generally Well-Tolerated

Epithalon has demonstrated a favorable safety profile across multiple clinical studies spanning decades of research. No serious adverse effects have been reported in published human studies at standard dosing regimens.

Injection Site Reactions

Mild redness, slight pain, or minor swelling at injection sites has been reported. These reactions are transient and self-limiting.

Drowsiness

Some users report mild drowsiness, particularly when dosed in the evening, which may be related to epithalon's melatonin-enhancing effects. This is generally considered beneficial for sleep quality.

Headache

Mild headaches have been occasionally reported, typically during initial use and resolving with continued treatment.

Theoretical Long-Term Considerations

While epithalon maintains p53 tumor suppressor function in research, the theoretical concern exists that any telomerase-activating agent could potentially promote growth of undetected malignancies. No evidence supports this concern in published studies, but it warrants ongoing vigilance in long-term use.

Limited Western Clinical Data

Most clinical data comes from Russian research institutions. While the body of evidence is substantial, it lacks the large-scale randomized controlled trials typical of Western pharmaceutical development.

Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.

Regulatory Status

Experimental

Epithalon is not approved by the FDA, EMA, or most Western regulatory authorities. It has been used clinically in Russia and several CIS countries where it was developed, under the research programs of the Saint Petersburg Institute of Bioregulation and Gerontology.

Professor Khavinson holds patents for epithalon and related peptide bioregulators in Russia and several other jurisdictions. The peptide has been the subject of over 100 published studies, but has not undergone formal Western clinical trial processes.

Epithalon is classified as a research peptide in most Western countries and is available from research chemical suppliers. It is not on the WADA prohibited list and does not fall under standard drug scheduling categories.

Research Studies

Peptide Promotes Overcoming of Hayflick Limit in Human Fibroblast Cell Cultures

Khavinson VK, Bondarev IE, Butyugov AA.

Experimental Gerontology
2003
View Source

Epitalon Peptide Activates Chromatin and Telomerase

Khavinson VK, Tendler SM, Vanyushin BF, et al.

Bulletin of Experimental Biology and Medicine
2003
View Source

Effect of Epithalamin on Lifespan Increase in Drosophila melanogaster

Anisimov VN, Khavinson VK.

Mechanisms of Ageing and Development
2002
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Pineal Peptides Restore Melatonin Production in Aged Rats

Anisimov VN, Khavinson VK, Popovich IG, et al.

Neuroendocrinology Letters
2003

Short Peptides Regulate Gene Expression and Longevity

Khavinson V, Linkova N, Diatlova A, et al.

International Journal of Molecular Sciences
2021
View Source
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