Epithalon

Epithalon (also written Epitalon) is a synthetic tetrapeptide with the sequence Ala-Glu-Asp-Gly (AEDG), the formula C14H22N4O9 and a molar mass of 390.35 g/mol. It was synthesized on the basis of the amino acid composition of epithalamin, a polypeptide extract of bovine pineal gland, and the same tetrapeptide was subsequently identified in a pineal polypeptide complex. The compound has been examined over roughly 25 years with in vitro, in vivo and in silico methods, although a 2025 review notes that physico-chemical and structural studies of the peptide remain limited.

Epithalon in the research literature

The most cited cell-culture work reported that adding epithalon to telomerase-negative fetal fibroblast cultures induced expression of the telomerase catalytic subunit, telomerase enzymatic activity and telomere elongation. A follow-up study from the same group reported that late-passage fetal lung fibroblasts exposed to the peptide regained telomere lengths comparable to early passages and continued dividing for at least ten passages beyond untreated controls. An independent 2025 study reported hTERT mRNA upregulation, increased telomerase activity and telomere extension in normal epithelial and fibroblast cell lines, whereas telomere extension in transformed cell lines was attributed to alternative lengthening of telomeres (ALT) activity.

Other studies have examined epithalon in rat pinealocyte culture, where it was reported to increase arylalkylamine-N-acetyltransferase (AANAT) and pCREB synthesis and melatonin levels in the medium, and in gingival mesenchymal stem cells, where it increased expression of neuronal differentiation markers and molecular modelling suggested binding to histone H1 sites.