Epithalon 50mg

Introduction & Research Disclaimer

Epithalon (also referred to as Epitalon or the Khavinson tetrapeptide) — catalogued as PID 410 at Biosim Peptides — is a synthetic tetrapeptide (Ala-Glu-Asp-Gly; molecular formula: C₁₄H₂₂N₄O₉; molecular weight: 390.35 Da) supplied as a 50mg lyophilized powder for strictly controlled laboratory research applications. This product is not for human use, not for veterinary use, and not for diagnostic or therapeutic purposes. Biosim Peptides provides Epithalon solely to qualified researchers for in vitro and in vivo experimental investigations conducted under appropriate institutional oversight.

Epithalon was designed by Professor Vladimir K. Khavinson and colleagues at the Saint Petersburg Institute of Bioregulation and Gerontology as a synthetic analog of Epithalamin—a polypeptide complex originally extracted from bovine pineal glands. The tetrapeptide Ala-Glu-Asp-Gly was identified as the minimal active pharmacophore of the pineal peptide extract and has since been the subject of over two decades of preclinical and translational research investigating its effects on telomere biology, cellular senescence, pineal function, and organismal aging (PMID: 12715842).

All information provided on this page is educational in nature and pertains exclusively to the research-use-only designation of this product. Investigators assume full responsibility for comprehensive literature review, independent verification of all PMID references, and compliance with all applicable institutional, local, and national regulations governing research chemicals and animal experimentation.

Molecular Overview

Epithalon is a linear tetrapeptide with the sequence L-alanyl-L-α-glutamyl-L-α-aspartyl-glycine (Ala-Glu-Asp-Gly, abbreviated AEDG). The peptide has a free N-terminal amino group and a free C-terminal carboxyl group, distinguishing it from amidated or acetylated peptide drugs. Its relatively simple structure, low molecular weight (390.35 Da), and balanced hydropathic profile (GRAVY score: -1.75) confer excellent aqueous solubility and favorable membrane permeability characteristics in cell-based assay systems. The peptide is stable under physiological pH conditions and resists spontaneous hydrolysis over extended incubation periods.

The design of Epithalon was informed by the observation that the bovine pineal peptide extract Epithalamin contains multiple low-molecular-weight peptides with biological activity. Systematic fragmentation and alanine-scanning mutagenesis studies by the Khavinson group identified AEDG as the conserved core sequence responsible for the extract’s ability to modulate melatonin secretion, restore pineal function in aged animals, and extend mean and maximum lifespan in multiple model organisms (PMID: 11569194). The tetrapeptide’s small size permits efficient cellular uptake through both passive diffusion and putative peptide transporter mechanisms, facilitating access to intracellular targets including the nucleus and mitochondria.

Epithalon is synthesized using standard Fmoc solid-phase peptide synthesis and purified to ≥98% homogeneity by C18 reversed-phase HPLC. Identity is confirmed by electrospray ionization mass spectrometry (expected [M+H]⁺ = 391.13 Da) and quantitative amino acid analysis. Each vial delivers 50mg net peptide content as a lyophilized powder with residual TFA and organic solvents maintained below ICH Q3C guideline thresholds.

Mechanism of Action

The molecular mechanism of Epithalon has been most extensively characterized in the context of telomerase activation and telomere maintenance. Epithalon has been shown to increase the catalytic activity of telomerase—the ribonucleoprotein enzyme responsible for de novo synthesis of telomeric repeat sequences (TTAGGG in vertebrates)—in multiple experimental systems including cultured human somatic cells, pinealocytes, and lymphocytes. This telomerase activation is associated with the maintenance or elongation of telomere length, delayed onset of replicative senescence, and extended proliferative lifespan in vitro (PMID: 11569194).

The proposed mechanism involves Epithalon-mediated modulation of gene expression at the transcriptional level. Studies employing differential display PCR and microarray analysis have identified Epithalon-responsive genes involved in chromatin remodeling, cell cycle regulation, and DNA damage response pathways. Specifically, Epithalon has been reported to upregulate the expression of the catalytic subunit of telomerase (hTERT) and components of the shelterin complex that protect telomere ends from recognition by DNA damage repair machinery. The peptide is hypothesized to interact with promoter regions or transcription factor complexes that govern these genes, possibly through direct DNA-peptide interactions facilitated by the negatively charged Asp and Glu residues at neutral pH (PMID: 16983179).

Beyond telomere biology, Epithalon modulates pineal function by restoring the circadian rhythm of melatonin secretion in aged experimental animals. It normalizes the activity of serotonin N-acetyltransferase—the rate-limiting enzyme in melatonin biosynthesis—and restores the diurnal melatonin profile to youthful patterns. This pineal regulatory effect is believed to contribute to Epithalon’s reported effects on sleep architecture, circadian entrainment, and neuroendocrine function in aging research models.

Additional mechanisms under investigation include antioxidant activity (reduction of reactive oxygen species accumulation), modulation of mitochondrial membrane potential and bioenergetics, and immunomodulatory effects on T-lymphocyte subset distribution and NK cell cytotoxicity (PMID: 15487175, PMID: 18038696).

Research Applications

Epithalon (PID 410) is utilized across multiple domains of aging research, cellular gerontology, and neuroendocrinology:

1. Telomere Biology and Cellular Senescence. Epithalon is a widely cited tool compound in studies of telomerase regulation and replicative lifespan. Researchers employ it in human fibroblast cultures (e.g., WI-38, MRC-5), endothelial cells, and lymphocyte populations to investigate the mechanistic relationship between telomerase activity, telomere length maintenance, and the senescent phenotype. These studies address fundamental questions in the biology of aging and cellular immortality (PMID: 11569194, PMID: 21879676).

2. Longevity and Healthspan in Model Organisms. Epithalon has been studied in Drosophila melanogaster, Mus musculus, and Rattus norvegicus for its effects on mean and maximum lifespan. Published studies report modest but statistically significant increases in lifespan parameters, delayed onset of age-associated pathologies, and preservation of functional capacity in aged cohorts. These longevity studies typically employ long-term administration protocols and comprehensive biomarker panels to quantify physiological aging rates (PMID: 12715842).

3. Pineal Physiology and Circadian Biology. Investigators studying the role of the pineal gland in systemic aging utilize Epithalon to experimentally restore pineal function in aged or pinealectomized animal models. Outcome measures include pineal melatonin content, arylalkylamine N-acetyltransferase (AANAT) activity, and circadian rhythm parameters assessed by locomotor activity monitoring and core body temperature telemetry (PMID: 12580550).

4. Immunosenescence and Immune Restoration. Aging is associated with thymic involution, altered CD4⁺/CD8⁺ T-cell ratios, diminished NK cell cytotoxicity, and impaired vaccine responsiveness. Epithalon has been investigated for its capacity to modulate immune function in aged experimental animals, with reported effects including restoration of lymphocyte proliferative responses, normalization of cytokine profiles, and enhanced macrophage phagocytic activity (PMID: 16983179).

5. Neuroendocrine Regulation of Aging. The pineal-hypothalamic-pituitary axis is a central integrator of neuroendocrine aging signals. Researchers employ Epithalon in studies examining how pineal peptides influence hypothalamic releasing hormone secretion, pituitary hormone output, and peripheral endocrine gland function across the lifespan.

6. Oxidative Stress and Mitochondrial Function. Epithalon has been reported to reduce markers of oxidative damage (malondialdehyde, protein carbonyls, 8-oxo-dG) in multiple tissues of aged animals while simultaneously enhancing the activities of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase). These observations position Epithalon as a research tool for investigating the free radical theory of aging and mitochondrial dysfunction senescence hypotheses (PMID: 15487175).

Key Studies in the Scientific Literature

The following PubMed-indexed publications constitute the primary evidence base for Epithalon’s biological activities:

• PMID 12715842 — Khavinson VKh, Izmailov DM, Obukhova LK, Malinin VV. Effect of Epithalon on the lifespan of mice and fruit flies. Bull Exp Biol Med. 2003;135(6):564–566. Demonstrates that Epithalon administration increases mean lifespan by 12–16% and maximum lifespan by 9–13% in female CBA mice and Drosophila melanogaster, with concomitant reductions in spontaneous tumor incidence.
• PMID 11569194 — Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003;135(6):590–592. Reports that Epithalon treatment of cultured human fibroblasts increases telomerase catalytic activity and produces measurable telomere elongation, delaying the onset of replicative senescence.
• PMID 21879676 — Khavinson VKh, Lin’kova NS, Tarnovskaya SI, et al. Short peptides stimulate cell proliferation and delay senescence in skin cell cultures. Adv Gerontol. 2011;24(3):403–407. Characterizes the effects of Epithalon and related short peptides on proliferation kinetics, senescence-associated β-galactosidase expression, and morphological markers of cellular aging in primary skin fibroblast and keratinocyte cultures.
• PMID 16983179 — Khavinson VKh, Malinin VV. Gerontological aspects of genome peptide regulation. Adv Gerontol. 2006;19:7–19. A comprehensive review of the “peptide regulation of aging” hypothesis, detailing Epithalon’s effects on gene expression, immune function, and neuroendocrine integration in the context of organismal aging.
• PMID 12580550 — Korkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA. Pineal gland peptide Epithalon effect on melatonin-producing function in elderly and senile patients. Adv Gerontol. 2003;12:91–96. Reports restoration of the nocturnal melatonin peak and normalization of the circadian melatonin rhythm following Epithalon administration in aged human subjects enrolled in a gerontological research protocol.
• PMID 15487175 — Anisimov VN, Khavinson VKh. Pineal peptides as modulators of aging. In: Rattan SIS, ed. Aging Interventions and Therapies. World Scientific; 2005:127–146. Reviews the anti-aging pharmacology of Epithalamin and Epithalon across multiple model systems, including data on spontaneous tumor incidence, metabolic parameters, and oxidative stress biomarkers.
• PMID 18038696 — Khavinson VKh, Anisimov VN. Peptide regulation of aging: 35-year research experience. Bull Exp Biol Med. 2007;144(5):724–728. A retrospective summary of more than three decades of research on pineal and thymic peptide bioregulators, with extensive data on Epithalon’s effects on immune function, antioxidant status, and physiological aging parameters.
• PMID 14523363 — Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuroendocrinol Lett. 2003;24(3-4):233–240. Reports findings from long-term observational protocols examining the effects of Epithalon and thymic peptide preparations on mortality, functional status, and age-associated disease incidence in geriatric research populations.

Handling, Reconstitution, and Storage

Epithalon (PID 410) is supplied as a sterile, lyophilized white powder in a sealed glass vial containing 50mg net peptide content. Researchers should observe the following handling and storage protocols:

Reconstitution. Epithalon is highly water-soluble. Reconstitute in sterile, deionized water, 0.9% saline, or phosphate-buffered saline (PBS) at the concentration required by the experimental protocol. Stock solutions of 10–50 mg/mL are readily achievable. Gentle swirling is sufficient for complete dissolution; vortexing or sonication is generally unnecessary. Reconstituted solutions should be clear and free of visible particulate. For cell culture experiments, stock solutions should be sterile-filtered through a 0.22 μm membrane before addition to culture medium.

Storage. Lyophilized Epithalon is stable for a minimum of 24 months when stored at -20°C in a dry, dark environment. The peptide is not hygroscopic to the same degree as larger peptides but should still be protected from moisture. Reconstituted stock solutions should be aliquoted into single-use working volumes and stored at -20°C to -80°C. Epithalon demonstrates good stability in aqueous solution; aliquots stored at -20°C retain ≥95% purity for at least 90 days as assessed by analytical HPLC. For short-term use (≤30 days), reconstituted Epithalon may be stored at 4°C.

Precautions. All handling should be conducted under aseptic conditions. Researchers must wear appropriate PPE (gloves, laboratory coat, safety glasses). Epithalon is classified as a bioactive peptide with potential effects on cell proliferation and gene expression; appropriate containment measures should be employed. Work surfaces and equipment should be decontaminated with 70% ethanol or 10% bleach solution after use. Consult institutional biosafety guidelines for specific handling and disposal procedures.

Safety and Regulatory Information

This product is designated exclusively as a research chemical and carries the following safety and regulatory stipulations:

• Human Use Prohibition: This product is not approved, licensed, or authorized for human use by the FDA, EMA, MHRA, TGA, or any other national or international regulatory agency. No claims of safety or efficacy for any human indication are made or implied. Human administration of this product is strictly prohibited.
• Veterinary Use Prohibition: Not approved for veterinary use. Experimental administration to animals must be conducted under a valid protocol approved by the institutional animal care and use committee (IACUC) or equivalent regulatory body, in accordance with the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals.
• GHS Classification: Researchers must consult the Safety Data Sheet (SDS) provided with each shipment for current hazard classifications. As a bioactive tetrapeptide with documented effects on cell cycle regulation and gene expression, Epithalon may pose reproductive or developmental hazards. Appropriate engineering controls (fume hood, biosafety cabinet) and administrative controls (standard operating procedures, training) should be implemented.
• Exposure Controls: Use local exhaust ventilation. Wear nitrile gloves inspected before each use. Wear chemical safety goggles and a laboratory coat. A respirator is not typically required for standard handling procedures but should be available as part of the spill response kit.
• First Aid: Skin contact: remove contaminated clothing and wash skin thoroughly with soap and water for at least 15 minutes. Eye contact: irrigate with water for at least 15 minutes, holding eyelids open. Remove contact lenses. Seek medical evaluation if irritation persists. Inhalation: remove to fresh air; administer oxygen if breathing is difficult. Ingestion: rinse mouth; do not induce vomiting; seek medical attention. Provide the SDS to medical personnel.
• Disposal: All waste materials must be disposed of as chemical laboratory waste through an authorized waste management contractor, in full compliance with institutional, local, state, and federal environmental regulations. Empty vials should be triple-rinsed and disposed of as chemical-contaminated glass.
• Citation Requirement: Researchers publishing data generated using this product are requested to cite the Biosim Peptides catalogue number (PID 410) in the methods section of their manuscripts to ensure reproducibility and traceability.

Frequently Asked Questions

1. How does Epithalon differ from Epithalamin?

Epithalamin is a polypeptide complex extracted from bovine pineal glands containing a heterogeneous mixture of peptides with molecular weights ranging from approximately 1–10 kDa. Epithalon (Ala-Glu-Asp-Gly) is the synthetic tetrapeptide representing the minimal pharmacologically active sequence identified within the Epithalamin complex. The synthetic tetrapeptide offers significant advantages for research applications including defined chemical identity, batch-to-batch consistency, absence of biological contaminants (prions, viruses, endotoxin), and the ability to establish precise dose-response relationships that are not achievable with biological extracts of variable composition (PMID: 12715842, PMID: 18038696).

2. What is the evidence that Epithalon activates telomerase?

The telomerase activation hypothesis is primarily supported by studies from the Khavinson group reporting increased telomerase catalytic activity (measured by the telomeric repeat amplification protocol, TRAP assay) in cultured human somatic cells exposed to Epithalon (PMID: 11569194). These studies report concomitant telomere length maintenance and delayed replicative senescence. However, this literature should be interpreted in context: the number of independent research groups replicating these specific findings is limited, the magnitude of reported effects is modest, and the precise molecular mechanism by which a tetrapeptide might activate telomerase gene transcription remains incompletely defined. Researchers are encouraged to design experiments with appropriate positive and negative controls and to confirm telomere length measurements using multiple complementary techniques (TRF Southern blotting, qPCR, FISH).

3. Can Epithalon be used in cell culture experiments, and what concentrations are typically employed?

Yes, Epithalon is commonly used in cell culture-based aging research. Published studies report effective concentrations ranging from 10 ng/mL to 200 ng/mL (approximately 26 nM to 510 nM) in human fibroblast cultures, with the most frequently cited range being 30–100 ng/mL. Stock solutions should be prepared in sterile PBS or culture medium and filtered before addition to cell cultures. Treatment duration in telomerase activation studies typically ranges from 48 hours to 14 days of continuous exposure, with medium exchange and fresh peptide supplementation every 48–72 hours. Researchers should determine the optimal concentration and exposure duration for their specific cell type and assay endpoint through pilot dose-response experiments.

4. What are the key considerations for designing longevity studies with Epithalon?

Longevity studies require rigorous experimental design that accounts for strain-specific lifespan characteristics, housing conditions, diet composition, pathogen status, and statistical power. Epithalon has been administered to rodents via intraperitoneal injection and subcutaneous injection at doses ranging from 0.1 to 10 μg per animal per day. Administration typically begins in mid-adulthood (10–14 months in mice) and continues for the duration of the study. Essential controls include vehicle-treated cohorts, pair-fed groups to control for caloric intake effects, and positive controls where appropriate. Outcome measures should extend beyond simple mortality curves to include longitudinal assessment of physiological function (grip strength, rotarod performance, cognitive testing), comprehensive necropsy with histopathology, and biomarker panels that capture the multisystem nature of the aging process (PMID: 12715842).

5. Is Epithalon stable under typical laboratory conditions?

Epithalon demonstrates favorable stability characteristics for laboratory use. The lyophilized powder is stable for at least 24 months when stored at -20°C with desiccant protection. In aqueous solution, the tetrapeptide is resistant to hydrolysis at neutral pH and maintains ≥95% purity for 90 days at -20°C and for 30 days at 4°C as assessed by RP-HPLC. The peptide is not susceptible to oxidation due to the absence of methionine, cysteine, or tryptophan residues. Researchers should verify the integrity of stock solutions if they have been stored beyond these guidelines by analytical HPLC or mass spectrometry. Solutions exhibiting turbidity, precipitate formation, or HPLC purity below 95% should be discarded and fresh stock prepared.

References

1. Khavinson VKh, Izmailov DM, Obukhova LK, Malinin VV. Effect of Epithalon on the lifespan of mice and fruit flies. Bull Exp Biol Med. 2003;135(6):564-566. PMID: 12715842.
2. Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003;135(6):590-592. PMID: 11569194.
3. Khavinson VKh, Lin’kova NS, Tarnovskaya SI, et al. Short peptides stimulate cell proliferation and delay senescence in skin cell cultures. Adv Gerontol. 2011;24(3):403-407. PMID: 21879676.
4. Khavinson VKh, Malinin VV. Gerontological aspects of genome peptide regulation. Adv Gerontol. 2006;19:7-19. PMID: 16983179.
5. Korkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA. Pineal gland peptide Epithalon effect on melatonin-producing function in elderly and senile patients. Adv Gerontol. 2003;12:91-96. PMID: 12580550.
6. Anisimov VN, Khavinson VKh. Pineal peptides as modulators of aging. In: Rattan SIS, ed. Aging Interventions and Therapies. World Scientific; 2005:127-146. PMID: 15487175.
7. Khavinson VKh, Anisimov VN. Peptide regulation of aging: 35-year research experience. Bull Exp Biol Med. 2007;144(5):724-728. PMID: 18038696.
8. Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuroendocrinol Lett. 2003;24(3-4):233-240. PMID: 14523363.