Epitalon
Epitalon (also written Epithalon) is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) derived from the pineal gland peptide epithalamin. Preliminary evidence from in vitro and animal studies indicates it may influence telomerase activity, antioxidant defense, circadian melatonin rhythms, and epigenetic chromatin remodeling. No randomized controlled trials in humans have been conducted, and all efficacy and safety data currently come from Tier 3 (animal and in vitro) sources.
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Quick facts
Suggested labs for this peptide class — educational reference only; not medical advice.
TL;DR
- Half-life: — — dosed —.
- Administered via —.
- Evidence base: animal model studies.
- Primary goals: longevity, sleep, anti-aging.
Primarily animal data
How it works
Epitalon is the synthetic tetrapeptide Ala-Glu-Asp-Gly (AEDG), originally isolated from bovine pineal epithalamin. In vitro evidence indicates that Epitalon increases telomere length in human cell lines through upregulation of telomerase or activation of the alternative lengthening of telomeres (ALT) pathway [3]. Separately, animal studies indicate that Epitalon activates telomerase and enhances bovine oocyte maturation and post-thawed embryo development in vitro [4]. In vitro evidence also indicates that Epitalon exhibits antioxidant activity and improves delayed wound healing in high-glucose-injured human retinal pigment epithelial cells, with antioxidant effects comparable to those of melatonin [10]. Animal studies indicate that Epitalon protects post-ovulatory mouse oocytes from aging-related damage in vitro at 0.1 mM concentration, again with antioxidant mechanisms proposed [11]. At the epigenetic level, mechanistic data point to Epitalon and related peptide bioregulators modifying chromatin condensation in lymphocytes from elderly individuals, reactivating repressed chromatin and deheterochromatinizing nucleolar organizer regions in cells from donors aged 75–88 years [src:be0b2b95-d849-47b9-ad82-945f79489992; src:8827b5d6-0ba0-4255-9b39-0b4cc140de51]. Preliminary in vitro evidence also suggests that Epitalon stimulates gene expression and protein synthesis during neurogenesis in human mesenchymal stem cells, potentially through epigenetic mechanisms [16]. Animal studies indicate that Epitalon increases mitochondrial staining (MitoTracker Red) approximately 1.5-fold in human pineal gland cells during senescence in vitro, suggesting effects on mitochondrial biogenesis or membrane potential [17]. In vitro evidence additionally indicates that Epitalon modulates monocyte and macrophage proliferative activity and inflammatory pathways in the THP-1 cell line [18]. In rat models, animal studies indicate that Epitalon decreases cathepsin B and D activity in liver and kidney lysosomes [19], reduces pancreatic amylase activity under various lighting conditions [20], modulates thyroid gland function and thyrotropic activity of the hypophysis [6], and stimulates proliferative activity in hypothalamic preoptic area explants at 2 ng/ml [21]. Animal studies further indicate that Epitalon may provide renoprotective effects against rhabdomyolysis-induced kidney injury by reducing oxidative stress and energetic imbalance [22]. Expert commentary suggests that Epitalon and Vilon regulate CCL11 (eotaxin) and HMGB1 (alarmin) gene expression, which are proposed molecular markers of aging [23]. All mechanisms described above derive from Tier 3 (animal or in vitro) sources; direct evidence linking these mechanisms to human physiology has not been established.
What the research says
Research summary content coming soon. Check the references section for indexed studies.
Protocol lifecycle
Before — Pre-cycle readiness
Readiness checklist
Evidence awareness
- Understand that all human-relevant Epitalon data are Tier 3 (animal/in vitro); no human RCTs exist.
- Acknowledge that efficacy and safety in humans remain unestablished.
Medical oversight
- Discuss use with a licensed clinician familiar with peptide research.
- Disclose all concurrent medications given the absence of drug–drug interaction data.
Regulatory awareness
- Epitalon has no FDA, EMA, or Health Canada approval; it is not an approved therapeutic in any major jurisdiction represented in this research packet.
- No evidence-based pre-use preparation guidance exists for humans; consult a qualified clinician before use.
- Baseline health assessment is prudent given the complete absence of controlled human safety data.
During — Active protocol
- No human clinical trial protocols exist to guide dosing, monitoring, or frequency during use.
- Animal study dosing (e.g., 1 mcg/mouse s.c. weekly in SAM mice [8]) cannot be reliably translated to human protocols.
After — Post-cycle
- No evidence-based cycling or post-use guidance exists for humans.
- Long-term effects following cessation are unstudied in humans.
Stacks it appears in
Epitalon is typically used as a standalone compound. Stack data coming soon.
Related peptides
Other compounds indexed on Pepteligence that share research tags with Epitalon. Educational context only.
Safety
Common side effects
- ·No controlled human data available to characterize common side effects.
Rare side effects
- ·No controlled human data available to characterize rare side effects.
- No controlled human data available to characterize serious adverse events; the absence of such data does not imply safety.
Contraindications
- ·No formal contraindications have been identified in controlled human studies; the absence of human safety data precludes definitive statements about safety in any specific population, including pregnancy, lactation, renal impairment, and hepatic impairment.
Community experiences
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Epitalon — at a glance
| Property | Epitalon | — |
|---|---|---|
| Half-life | — | — |
| Route | — | — |
| Typical dose | See research context | — |
| Mechanism | Epitalon is the synthetic tetrapeptide Ala-Glu-Asp-Gly (AEDG), originally isolated from bovine pineal epithalamin. In vitro evidence indicates that Epitalon increases telomere length in human cell lines through upregulation of telomerase or activation of the alternative lengthening of telomeres (ALT) pathway. Separately, animal studies indicate that Epitalon activates telomerase and enhances bovine oocyte maturation and post-thawed embryo development in vitro. In vitro evidence also indicates that Epitalon exhibits antioxidant activity and improves delayed wound healing in high-glucose-injured human retinal pigment epithelial cells, with antioxidant effects comparable to those of melatonin. Animal studies indicate that Epitalon protects post-ovulatory mouse oocytes from aging-related damage in vitro at 0.1 mM concentration, again with antioxidant mechanisms proposed. At the epigenetic level, mechanistic data point to Epitalon and related peptide bioregulators modifying chromatin condensation in lymphocytes from elderly individuals, reactivating repressed chromatin and deheterochromatinizing nucleolar organizer regions in cells from donors aged 75–88 years [src:be0b2b95-d849-47b9-ad82-945f79489992; src:8827b5d6-0ba0-4255-9b39-0b4cc140de51]. Preliminary in vitro evidence also suggests that Epitalon stimulates gene expression and protein synthesis during neurogenesis in human mesenchymal stem cells, potentially through epigenetic mechanisms. Animal studies indicate that Epitalon increases mitochondrial staining (MitoTracker Red) approximately 1.5-fold in human pineal gland cells during senescence in vitro, suggesting effects on mitochondrial biogenesis or membrane potential. In vitro evidence additionally indicates that Epitalon modulates monocyte and macrophage proliferative activity and inflammatory pathways in the THP-1 cell line. In rat models, animal studies indicate that Epitalon decreases cathepsin B and D activity in liver and kidney lysosomes, reduces pancreatic amylase activity under various lighting conditions, modulates thyroid gland function and thyrotropic activity of the hypophysis, and stimulates proliferative activity in hypothalamic preoptic area explants at 2 ng/ml. Animal studies further indicate that Epitalon may provide renoprotective effects against rhabdomyolysis-induced kidney injury by reducing oxidative stress and energetic imbalance. Expert commentary suggests that Epitalon and Vilon regulate CCL11 (eotaxin) and HMGB1 (alarmin) gene expression, which are proposed molecular markers of aging. All mechanisms described above derive from Tier 3 (animal or in vitro) sources; direct evidence linking these mechanisms to human physiology has not been established. | — |
| Evidence strength | animal | anecdotal |
| Primary goal | longevity | — |
Frequently asked questions
What is Epitalon?
How does Epitalon work?
What is Epitalon used for?
Is Epitalon FDA-approved?
What are common dosages of Epitalon?
How is Epitalon administered?
What are common side effects of Epitalon?
Are there safety concerns with Epitalon?
Is Epitalon related to the pineal gland?
Can Epitalon be combined with other compounds?
Is Epitalon legal?
What does the research on Epitalon show overall?
References
- [1]
Overview of Epitalon-Highly Bioactive Pineal Tetrapeptide with Promising Properties.
Araj Szymon Kamil, Brzezik Jakub, Mądra-Gackowska Katarzyna et al.
International journal of molecular sciences · 2025 · PMID 40141333
- [2]
Therapeutic peptides in gerontology: mechanisms and applications for healthy aging.
Mavrych Volodymyr, Shypilova Inna, Bolgova Olena
Frontiers in aging · 2026 · PMID 42021992
- [3]
Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity.
Al-Dulaimi Sarah, Thomas Ross, Matta Sheila et al.
Biogerontology · 2025 · PMID 40908429
- [4]
Epitalon-activated telomerase enhance bovine oocyte maturation rate and post-thawed embryo development.
Ullah Safeer, Haider Zaheer, Perera Chalani Dilshani et al.
Life sciences · 2025 · PMID 39788414
- [5]
[Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people].
Korkushko O V, Lapin B A, Goncharova N D et al.
Advances in gerontology = Uspekhi gerontologii · 2007 · PMID 17969590
- [6]
[Effect of preparations melatonin and epitalon on the age-related dynamics of thyrotrophic activity of the hypophysis and thyroid gland function in different light regimes].
Vinogradova I A
Advances in gerontology = Uspekhi gerontologii · 2009 · PMID 20405731
- [7]
Effect of epitalon on the lifespan increase in Drosophila melanogaster.
Khavinson V K, Izmaylov D M, Obukhova L K et al.
Mechanisms of ageing and development · 2000 · PMID 11087911
- [8]
[Effect of epitalon and melatonin on life span and spontaneous carcinogenesis in senescence accelerated mice (SAM)].
Anisimov V N, Popovich I G, Zabezhinskij M A et al.
Voprosy onkologii · 2005 · PMID 15909815
- [9]
Stressors and antistressors: how do they influence life span in HER-2/neu transgenic mice?
Semenchenko Ganna V, Anisimov Vladimir N, Yashin Anatoli I
Experimental gerontology · 2004 · PMID 15501020
- [10]
The Antioxidant Tetrapeptide Epitalon Enhances Delayed Wound Healing in an in Vitro Model of Diabetic Retinopathy.
Gatta Marco, Dovizio Melania, Milillo Cristina et al.
Stem cell reviews and reports · 2025 · PMID 40493162
- [11]
Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro.
Yue Xue, Liu Sai-Li, Guo Jia-Ni et al.
Aging · 2022 · PMID 35413689
- [12]
[Age-related changes of exercise capacity and some biochemical indices of rat muscles under influence of different light conditions and pineal preparations].
Vingradova I A, Iliukha V A, Fedorova A S et al.
Advances in gerontology = Uspekhi gerontologii · 2007 · PMID 17969589
- [13]
[Comparative study of the effects of melatonin and epitalon on the protracted memory under the shuttle labyrinth test conditions in rats in the course of aging].
Vinogradova I A
Eksperimental'naia i klinicheskaia farmakologiia · 2006 · PMID 17209456
- [14]
Anti-aging peptide bioregulators induce reactivation of chromatin.
Lezhava T, Monaselidze J, Kadotani T et al.
Georgian medical news · 2006 · PMID 16705247
- [15]
EPIGENETIC MODIFICATION UNDER THE INFLUENCE OF PEPTIDE BIOREGULATORS ON THE 'OLD' CHROMATIN.
Lezhava T, Jokhadze T, Monaselidze J et al.
Georgian medical news · 2023 · PMID 37042594
- [16]
AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism.
Khavinson Vladimir, Diomede Francesca, Mironova Ekaterina et al.
Molecules (Basel, Switzerland) · 2020 · PMID 32019204
- [17]
[The influence of AEDG and KE peptides on mitochondries stain and L7A ribosomes protein expression during human pineal gland and thymus cell senescence in vitro.]
Ivko O M, Drobintseva A O, Leont'eva D O et al.
Advances in gerontology = Uspekhi gerontologii · 2020 · PMID 33342107
- [18]
Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line.
Avolio Francesco, Martinotti Stefano, Khavinson Vladimir Kh et al.
International journal of molecular sciences · 2022 · PMID 35408963
- [19]
[Effect of age, different light conditions, melatonin, and epitalon on lysosomal proteinase activity in the liver and kidneys of rats].
Rendakov N L, Tiutiunnik N N, Vinogradova I A
Advances in gerontology = Uspekhi gerontologii · 2006 · PMID 17152724
- [20]
[Influence of light regimens, melatonin, and epitalon on amylase activity in the pancreas and small intestine in rats of different age].
Svechkina E B, Tiutiunnik N N, Vinogradova I A
Advances in gerontology = Uspekhi gerontologii · 2006 · PMID 17152723
- [21]
[The effect of pineal peptide preparations on proliferative activity in organotypic culture of the preoptic hypothalamus area].
Miliutina Iu P, Kozina L S, Arutiunian A V et al.
Advances in gerontology = Uspekhi gerontologii · 2007 · PMID 18383712
- [22]
[Main mechanisms of rhabdomyolysis-caused kidney injury and their correction by organospecific peptides].
Zamorskij I I, Shchudrova T S
Biofizika · 2014 · PMID 25730989
- [23]
[Peptides and CCL11 and HMGB1 as molecular markers of aging: literature review and own data].
Khavinson V Kh, Kuznik B I, Tarnovskaia S I et al.
Advances in gerontology = Uspekhi gerontologii · 2014 · PMID 25826983
- [?]
Short Exogenous Peptides Regulate Expression of CLE, KNOX1, and GRF Family Genes in Nicotiana tabacum.
Fedoreyeva L I, Dilovarova T A, Ashapkin V V et al.
Biochemistry. Biokhimiia · 2017 · PMID 28371610
- [?]
Melatonin and pineal gland peptides are able to correct the impairment of reproductive cycles in rats.
Arutjunyan Alexander, Kozina Ljudmila, Milyutina Yulia et al.
Current aging science · 2012 · PMID 23237594
- [?]
[Characteristics of the pineal gland and thymus relationship in aging].
Lin'kova N S, Poliakova V O, Kvetnoi I M et al.
Advances in gerontology = Uspekhi gerontologii · 2011 · PMID 21809618
- [?]
[Influence of peptides from pineal gland on thymus function at aging].
Lin'kova N S, Poliakova V O, Trofimov A V et al.
Advances in gerontology = Uspekhi gerontologii · 2010 · PMID 21510076
- [?]
Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas.
Goncharova N D, Vengerin A A, Khavinson V Kh et al.
Experimental gerontology · 2005 · PMID 15664732
- [?]
[Effect of epitalon on the immunity and hemostasis in hypophysectomized chicken and old hens].
Kuznik B I, Pateiuk A V, Khavinson V Kh et al.
Advances in gerontology = Uspekhi gerontologii · 2004 · PMID 15490730