Epitalon (Epithalon)

What Is Epithalon?

Epithalon (also called Epitalon or Epithalone; synthetic analog of the pineal extract Epithalamin) is a short tetrapeptide that has been widely studied in experimental gerontology and neuroendocrine research.

It is primarily investigated as a tool compound in:

• Telomerase and telomere biology
• Melatonin secretion and circadian rhythm regulation
• Epigenetic / chromatin remodeling and gene expression
• Tumor biology, immune aging, and microvascular function

The bulk of available data comes from:

• In vitro cell and tissue studies
• Rodent models of aging and tumorigenesis
• Limited human studies conducted mainly in Russia and Eastern Europe

Epithalon is not an approved drug and is supplied strictly for research use.

Epithalon Structure

• Sequence: Ala–Glu–Asp–Gly (AEDG)
• Type: Synthetic tetrapeptide
• Molecular formula: C₁₄H₂₂N₄O₉
• Approx. molecular weight: 390.35 g/mol
• Related to: Pineal extract Epithalamin

Telomerase Activation & Cellular Aging

Normal human somatic cells can divide only a finite number of times (the Hayflick limit, ~60–80 divisions), largely due to telomere shortening:

• Telomeres protect chromosome ends; with each division, they shorten.
• When telomeres reach a critical minimum, cells enter senescence, stop dividing, and may contribute to age-related tissue decline.

The telomerase enzyme can extend telomeric DNA and increase the replicative lifespan of some cells in vitro.

Research with Epithalon has reported:

• Upregulation of telomerase expression and activity in selected human cell lines
• Delayed onset of cellular senescence and extended proliferative capacity under controlled conditions

These properties make Epithalon a useful probe for telomere dynamics and cellular lifespan studies. The long‑term systemic consequences of such modulation in vivo remain incompletely defined.

DNA Regulation, Chromatin, and Gene Expression

Experimental work, particularly from Russian gerontological institutes, suggests that Epithalon may:

• Influence chromatin structure, altering DNA accessibility
• Reactivate genes that became transcriptionally silent with age
• Modulate genes involved in:
• Development and differentiation
• Immune function
• Cellular maintenance and stress responses

In older human cohorts (ages ~60–74 years) receiving courses of pineal peptide preparations (containing or related to Epithalon) over 2–3 years:

• Reported functional benefits (e.g., immune and clinical parameters) persisted for up to 3 years after the last course.
• Authors proposed relatively durable epigenetic and chromatin-level changes as a mechanistic basis.

These interpretations remain hypothesis‑generating and require larger, independent, controlled trials.

Tumor Growth & Immune Modulation (Preclinical)

A major focus of Epithalon research has been its role in spontaneous tumor development in aged rodents:

• Long-term administration of pineal peptide preparations containing Epithalon has been associated with:
• Reduced tumor incidence in the pineal gland and colon
• Approximate 2.6–2.8× reductions in certain tumor types
• Around 40% lower overall tumor frequency in some study designs

In cell-based systems and small clinical series, Epithalon has been linked to:

• Shifts in gene expression patterns consistent with enhanced genomic stability
• Reported improvements in immune function and survival measures in older or immunocompromised subjects receiving periodic peptide courses

However:

• Most results come from a single research network and limited geographic region.
• Telomerase activation can be double‑edged, with possible pro‑tumor and anti‑tumor effects depending on context.

Epithalon should therefore be treated purely as a research tool in oncology and immunogerontology, not as an anticancer therapy.

Melatonin Secretion & Circadian Rhythms

Aging is associated with reduced pineal gland activity and declining melatonin output, along with disruption of circadian rhythms. These changes correlate with:

• Metabolic dysregulation
• Immune impairment
• Increased risk of certain malignancies

Rodent studies using pineal extracts containing Epithalon (e.g., PESI, “pineal extract of substance inhibiting aging”) and synthetic Epithalon have shown:

• Restoration or enhancement of melatonin secretion following age-related decline
• Improved stability of circadian rhythms
• Extension of lifespan under certain experimental conditions

These data support the hypothesis that normalization of melatonin and circadian signaling is one component of Epithalon’s reported geroprotective effects in preclinical models.

Ocular & Microvascular Aging

Age-related visual decline often involves:

• Reduced retinal and choroidal perfusion
• Microvascular degeneration and tissue remodeling

Animal studies with Epithalon and related pineal peptides have reported:

• Increased retinal blood flow in older animals
• Partial reversal of an estimated ~40% age-related decrease in ocular microcirculation

Improved microvascular function may:

• Enhance nutrient and oxygen delivery to retinal tissues
• Support more efficient metabolic waste removal

These findings are preliminary but suggest value for Epithalon as a research tool in ocular and microvascular aging models.

Research Background: Prof. Vladlen Khavinson

Much of the foundational Epithalon work is associated with Prof. Vladlen Khavinson, a leading researcher in peptide bioregulation:

• President, European Region of the International Association of Gerontology and Geriatrics (IAGG)
• Director, Saint Petersburg Institute of Bioregulation and Gerontology, Russia
• Author or co-author of numerous studies on:
• Short peptide regulation of genome function
• Peptide-based geroprotective and oncological strategies
• Early-stage human applications of peptide interventions

While influential, this body of research still requires broad independent replication and integration into international standards.

Article Author

This product description and literature summary were researched, revised, and organized by Dr. Logan, M.D.

• M.D. – Case Western Reserve University School of Medicine
• Additional certification in molecular biology

Selected References

1. Khavinson VK, Anisimov VN, Zabezhinskii MI, et al. Effect of the pineal peptide preparation epithalamin on the life span and pineal and serum melatonin level in old rats. Ann N Y Acad Sci. 1994;719:393–407.
2. Khavinson VK, Chalisova GM, Ashapkin N, Shataeva N, Cartwright A. Mechanisms underlying the immunomodulatory actions of pineal peptides and their use in cancer control strategy. Biol Today. 2012;8:13–20.
3. Khavinson VK, Morozov VG, Abisheva IA, Semenchenko SI, Vanyushin SV. Effect of pineal peptide preparation epithalamin on the proliferation and the development of spontaneous tumors in old rodents. Front Aging Neurosci. 2013;5:128.
4. Khavinson VK, Malinin AV. Gerontological aspects of genome peptide regulation: the role of short peptides. Biogerontology. 2005;6(3):191–201.
5. Khavinson VK, Aliakina IV, Ryzhak GA, Muradian N, Anisimov V, Suchkov RA. Effect of epithalamin on the life span and hypothalamus resistance to aging. Adv Gerontol. 2005;8(2):109–114.
6. Dave S, Kavanagh R, Sheridan J, et al. The association between body mass index and tumor size in soft tissue sarcomas and GIST-soft tumors. Medicine (Baltimore). 2016;95(34):e4578.
7. Khavinson VK, Shataeva LK, Chalisova KA. Effect of regulatory peptides on DNA synthesis in irradiated and non-irradiated splenocytes. Bull Exp Biol Med. 1995;119(1):79–81.
8. Kubanova DV, et al. Deconvolution effect of the pineal-gland peptide on the fatty acid cholesterol esters in the choroidal and ciliary body in albino rats and their correlation with degenerative processes. Tsitologiia. 2008;50(9):779–782.
9. Khavinson V, Goncharova B, Lapin N. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescence accelerated OXYS rats. Neuroendocrinol Lett. 2001;22(4):251–254.
10. Chalisova NI, Litivina ME, Shchukin MM, Drozdov AG, Ryzhak GA, Khavinson VK. Effect of peptide epitalon on microvascular reactions and their role in age-dependent reorganization of tissues. Bull Exp Biol Med. 2006;141(4):452–455.
11. Linke NV, Pankova AA. Peptide regulation of skin fibroblast functions during aging in vitro. Bull Exp Biol Med. 2009;148(1):151–155.
12. Vinogradova IV, Ruslova VV, Zabezhinskii MV, et al. The geroprotective property of epithalon and metformin during aging. Adv Gerontol. 2017;30(1):93–104.