Epithalon
Published research and evidence base
Epithalon (also written Epitalon) is a synthetic tetrapeptide, Ala-Glu-Asp-Gly (AEDG), derived from the pineal gland extract preparation Epithalamin. Published work reports induction of telomerase activity and telomere elongation in cultured human cells, modulation of circadian and pineal gene expression, antioxidant effects, and extension of median lifespan in Drosophila and rodent models. The great majority of this literature originates from a single Russian research group, with a small number of independent in vitro replications appearing between 2022 and 2025. No registered, placebo-controlled randomised trial of the tetrapeptide in humans has been published in the indexed literature.
- Studies cited
- 15
- Published 2023+
- 8
- Newest paper
- 2026
- Last reviewed
- Aug 2026
Recurring themes in the literature
- telomerase induction
- telomere length
- pineal gland and melatonin regulation
- circadian clock gene expression
- geroprotection and lifespan
- oxidative stress and antioxidant activity
- epigenetic chromatin modification
- cellular senescence markers
Compound identifiers
- CAS
- 307297-39-8
- PubChem
- 219042
Recommended by an FDA advisory committee.
On 23–24 July 2026 the FDA’s Pharmacy Compounding Advisory Committee considered Epithalon, heard under the name Epitalon, for the 503A Bulks List and recommended its addition. Heard under the spelling Epitalon and recommended on a divided vote. Published accounts of the meeting differ on the exact tally, so none is quoted here.
This is not an approval. The committee advises; it does not decide. The recommendation is not binding, the FDA has not completed the rulemaking that would formally change anything, and inclusion on the 503A Bulks List is not equivalent to FDA approval of a drug. The list also governs pharmacy compounding for patients, which is a separate activity from research-use-only supply.
What the July 2026 advisory vote actually did sets out the process, the other compounds heard, and the four things the vote is routinely misreported as meaning.
What Epithalon is, chemically.
- Molecular formula
- C14H22N4O9
- Molecular weight
- 390.35 g/mol
- CAS number
- 307297-39-8
- PubChem CID
- 219042
Epitalon, Epithalone
These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.
15 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Human clinical2024· Russian (English abstract)
Peptidergic regulation of expression of cellular aging marker proteins in buccal epithelium
Ivko OM, et al. · Advances in Gerontology (Uspekhi Gerontologii) · buccal epithelial cells sampled from human subjects with disturbed melatonin secretion
AEDG peptide administration was associated with reduced expression of the senescence-associated proteins p16, p21 and p53 in buccal epithelium. Circadian gene expression and melatonin secretion indices shifted toward values seen in younger subjects.
- 02Human clinical2003
Peptides of pineal gland and thymus prolong human life
Khavinson VKh, Morozov VG · Neuro Endocrinology Letters · 266 elderly subjects followed 6-8 years, thymic (Thymalin) and pineal (Epithalamin) peptide preparations
The authors reported reduced mortality in peptide-treated elderly cohorts relative to controls over 6 to 8 years of follow-up, with the largest reduction in the combined Thymalin plus Epithalamin group. The report describes an open, non-randomised observational design and used the pineal extract preparation Epithalamin rather than the synthetic AEDG tetrapeptide.
- 03Animal in vivo2003
Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice
Anisimov VN, et al. · Biogerontology · female Swiss-derived SHR mice, lifelong monthly subcutaneous dosing, lifespan and tumour incidence study
Epitalon-treated female SHR mice showed an increase in maximum lifespan of approximately 12 percent relative to controls. Incidence of leukaemia was reduced, and the authors reported no increase in total spontaneous tumour incidence.
- 04Animal in vivo2001
Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys
Khavinson V, Goncharova N, Lapin B · Neuro Endocrinology Letters · old rhesus monkeys (Macaca mulatta), melatonin and cortisol circadian profiling
Epitalon administration increased evening melatonin output in aged monkeys whose nocturnal melatonin rise had flattened. Disturbed circadian cortisol profiles were reported to move toward the pattern seen in young animals.
- 05Animal in vivo2000
Effect of epitalon on the lifespan increase in Drosophila melanogaster
Khavinson VK, et al. · Mechanisms of Ageing and Development · Drosophila melanogaster, peptide administered during larval development
Epitalon added to the medium during development increased adult Drosophila lifespan by roughly 11 to 16 percent. The effect was reported to be independent of concentration across the very low doses tested.
- 06In vitro2025
Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity
Al-Dulaimi S, Thomas R, Matta S, Roberts T · Biogerontology · human normal and breast cancer cell lines; qPCR telomere length assay and immunofluorescence
Epitalon exposure was associated with increased telomere length in the cell lines tested, attributed to telomerase upregulation in normal cells and to alternative lengthening of telomeres (ALT) activity in cancer lines. A correction to this article was published in Biogerontology in November 2025 (PMID 41240216, doi 10.1007/s10522-025-10326-8).
- 07In vitro2025
The Antioxidant Tetrapeptide Epitalon Enhances Delayed Wound Healing in an in Vitro Model of Diabetic Retinopathy
Gatta M, et al. · Stem Cell Reviews and Reports · human retinal pigment epithelial cells under high-glucose conditions (in vitro diabetic retinopathy model)
High-glucose culture delayed scratch-wound closure and raised reactive oxygen species in retinal pigment epithelial cells. Epitalon treatment restored wound closure and reduced markers of hyperglycaemia-induced epithelial-mesenchymal transition and fibrosis.
- 08In vitro2025
Epitalon-activated telomerase enhance bovine oocyte maturation rate and post-thawed embryo development
Ullah S, et al. · Life Sciences · bovine oocytes and cumulus cells; in vitro maturation and post-thaw embryo culture
Epitalon supplementation increased telomerase activity in bovine oocytes and cumulus cells and raised in vitro maturation rates. Post-thaw blastocyst development and mitochondrial function measures were also improved relative to untreated controls.
- 09In vitro2024
Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes
Kraskovskaya N, et al. · International Journal of Molecular Sciences · induced neurons transdifferentiated from human fibroblasts of aged donors
AEDG and related short peptides increased dendritic outgrowth in induced neurons derived from aged donor fibroblasts. Markers of oxidative DNA damage were reduced in treated cultures.
- 10In vitro2023
Epigenetic Modification Under the Influence of Peptide Bioregulators on the "Old" Chromatin
Lezhava T, Jokhadze T, Monaselidze J, et al. · Georgian Medical News · cultured lymphocytes from elderly human donors
Peptide bioregulators including the AEDG tetrapeptide induced decondensation of constitutive heterochromatin in lymphocytes from elderly donors. Each peptide acted selectively on particular chromosome regions rather than uniformly across the genome.
- 11In vitro2022
Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro
Yue X, et al. · Aging (Albany NY) · mouse oocytes cultured 24 h post-ovulation
Epitalon reduced reactive oxygen species accumulation and preserved mitochondrial membrane potential in post-ovulatory aged mouse oocytes. Spindle and chromosome abnormalities associated with post-ovulatory ageing were attenuated in treated oocytes.
- 12In vitro2020
AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism
Khavinson V, et al. · Molecules · human gingival mesenchymal stem cells undergoing neuronal differentiation, plus molecular docking
AEDG peptide increased expression of neurogenesis markers including Nestin, GAP43, beta-tubulin III and doublecortin during neuronal differentiation. Molecular modelling indicated binding of the peptide to histone proteins and to DNA, which the authors proposed as an epigenetic mechanism.
- 13In vitro2003
Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells
Khavinson VKh, et al. · Bulletin of Experimental Biology and Medicine · human fetal fibroblast culture at the Hayflick limit
Addition of Epithalon to human somatic cell cultures induced telomerase activity and telomere elongation. The authors reported that treated cultures underwent additional population doublings beyond the expected replicative limit. This is the foundational report underlying subsequent telomerase claims for the peptide.
- 14Review2026
Therapeutic peptides in gerontology: mechanisms and applications for healthy aging
Mavrych V, et al. · Frontiers in Aging · narrative review of nine therapeutic peptides used or investigated in aging research, including Epithalon
The review placed Epithalon among investigational geroprotective peptides whose mechanistic rationale rests largely on preclinical data. The authors concluded that investigational peptides in this class require validation through well-designed clinical trials before therapeutic claims can be supported.
- 15Review2025
Overview of Epitalon-Highly Bioactive Pineal Tetrapeptide with Promising Properties
Araj SK, et al. · International Journal of Molecular Sciences · narrative review covering approximately 25 years of Epitalon literature
The review summarised reported geroprotective, neuroendocrine, antioxidant and neuroprotective effects of the AEDG tetrapeptide. The authors stated that substantial gaps remain in the understanding of its molecular mechanism and clinical relevance.
What this evidence does not establish.
The Epithalon evidence base is dominated by a single research group, the St Petersburg Institute of Bioregulation and Gerontology (Khavinson and colleagues), is largely published in Russian-language journals such as Uspekhi Gerontologii and Byulleten Eksperimentalnoi Biologii i Meditsiny, and has seen very little independent replication; the small number of independent papers are in vitro only. There are no published randomised, placebo-controlled, registered clinical trials of the synthetic AEDG tetrapeptide, the human longevity reports used the pineal extract preparation Epithalamin under non-randomised open designs, and human pharmacokinetics, dose-response and long-term safety, including any oncological risk from telomerase induction, remain uncharacterised.
Common questions about the research.
- What is Epithalon?
Epithalon is a synthetic tetrapeptide with the sequence Ala-Glu-Asp-Gly, abbreviated AEDG. It is the defined single-sequence analogue of Epithalamin, a pineal-gland polypeptide extract studied in Russian gerontology research, and it is supplied here as a lyophilised research material.
- What does the telomerase research actually show?
One frequently cited in-vitro study reported that adding the peptide to telomerase-negative human fetal fibroblast cultures induced expression of the telomerase catalytic subunit, measurable enzymatic activity, and telomere elongation. That is a cell-culture observation. It has not been shown to translate into any clinical outcome, and nothing here should be read as a claim about ageing in humans.
- How does Epithalon differ from Pinealon?
Both are short bioregulator peptides from the same Russian research programme, but they are different sequences with different literature. Epithalon is the tetrapeptide Ala-Glu-Asp-Gly studied mainly in pineal and telomere contexts; Pinealon is the tripeptide Glu-Asp-Arg studied mainly in neuronal models.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.