Epithalon

Also known as: Epitalon, Epithalone, AEDG peptide, Ala-Glu-Asp-Gly

Evidence: Preclinical

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Overview

Synthetic tetrapeptide Ala-Glu-Asp-Gly (PubChem CID 219042); human cell cultures show telomerase induction, and in mice it raised maximum but not mean lifespan.

Epitalon (AEDG) is a synthetic tetrapeptide designed from the amino acid composition of Epithalamin, a bovine pineal gland extract, and later reported in pineal polypeptide complex. The headline findings are in cell culture: added to telomerase-negative human fetal fibroblasts it induced hTERT expression, telomerase activity and telomere elongation (Khavinson 2003), and senescing fibroblasts made about 10 extra passages past the Hayflick limit (Khavinson 2004). An independent 2025 group reproduced dose-dependent telomere lengthening in normal human cells and found ALT activation in cancer lines (Al-Dulaimi 2025). In mice given 1 mcg per animal on 5 days a month for life, mean lifespan did not change (Anisimov 2003). No controlled trial of the synthetic peptide has been published; the long-term human studies used the bovine extract.

Benefits

Telomerase induction and telomere elongation (human fibroblasts in vitro), extra population doublings in senescing human cells (in vitro), raised maximum lifespan and 6-fold fewer leukemias (mouse), melatonin rhythm normalization (reported for the bovine pineal extract, not the peptide)

Dosing reference

Research dose: 5 to 10 mg daily for 10 to 20 days: research-community range, no published human dose-finding study
Range: 5000 to 10000 mcg, Daily (10-20 day cycle)
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 10 mg, 50 mg

Subcutaneous or intramuscular in research use; intranasal and intramuscular routes were both used in rodent studies. Cycling of 10 to 20 days, 2 to 3 times a year, is community convention with no published basis. Mouse geroprotection studies used 1 mcg per animal, roughly 30 to 40 mcg/kg, on 5 consecutive days each month for life (Anisimov 2003), which is a different schedule from any human protocol.

Mechanism

Proposed mechanisms, all from cell culture and rodent work. In telomerase-negative human fibroblasts AEDG induced expression of the telomerase catalytic subunit and measurable telomerase activity, with telomere elongation (Khavinson 2003); a 2025 independent replication found the same in normal cells through hTERT upregulation, and separately ALT activation in breast cancer lines (Al-Dulaimi 2025). Molecular modelling and binding work from the same group proposes direct interaction of short peptides with DNA promoter regions and with LAT and PEPT family transporters for cell entry; neither is established. Effects on melatonin are not settled: perifused rat pineal glands showed no change in melatonin secretion at 10 to the minus 4 through 10 to the minus 6 M (Djeridane 2003), while the extract studies in elderly subjects report rhythm normalization.

Evidence

Preclinical: animal or in vitro data only

Induced telomerase catalytic subunit expression, telomerase activity and telomere elongation in telomerase-negative human fetal fibroblasts (Khavinson et al., 2003)
Senescing human fetal lung fibroblasts treated at passage 34 elongated their telomeres and completed about 10 further passages, past the Hayflick limit (Khavinson et al., 2004)
Independent replication in 2025: dose-dependent telomere lengthening through hTERT and telomerase upregulation in normal human cells, and ALT activation in breast cancer lines (Al-Dulaimi et al., 2025)
In female SHR mice dosed for life, mean lifespan and total tumor incidence did not change; the last decile of survivors gained 13.3%, maximum lifespan 12.3%, bone marrow chromosome aberrations fell 17.1% and leukemia incidence was 6-fold lower (Anisimov et al., 2003)
Perifused pineal glands from young and old rats showed no change in melatonin secretion at any tested concentration, with or without isoproterenol (Djeridane et al., 2003)
Human-trial status: no controlled trial of the synthetic tetrapeptide has been published and none is registered on ClinicalTrials.gov. Human exposure data are limited to in vitro work on donor lymphocytes; the 12-year randomized geroprotection study in elderly coronary patients used Epithalamin, the bovine pineal extract, not AEDG (Korkushko et al., 2006)

References

Side effects

No controlled safety study of the synthetic peptide exists in any species at human-relevant doses. Lifelong dosing in mice produced no change in food consumption, body weight or total tumor incidence, and the authors described long-term administration as well tolerated in that model (Anisimov 2003). The randomized human studies reporting no adverse effects used Epithalamin, the bovine pineal extract. Commonly reported by users: injection-site irritation. One 2015 regulatory analysis identified AEDG in two illegal pharmaceutical preparations, so product identity and purity are a practical risk.

Storage

Storage: Refrigerated (2-8°C)
Lyophilized: 24+ months at room temperature
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: No pharmacokinetic study in any species has been published; the 2025 review of 25 years of Epitalon research reports no absorption, distribution or elimination data
Bioavailability: Not measured in any species. Rodent studies dosed intramuscularly and intranasally and reported central effects by both routes, with onset at 24 h intramuscularly and 1.5 h intranasally
Molecular weight: 390.35 Da
Sequence: AEDG

Stacks with

DSIP