Epitalon

In cultured human cells — normal epithelial cells and fibroblasts alongside the 21NT and BT474 breast cancer lines — Epitalon produced dose-dependent telomere lengthening, driven in the normal cells by increased hTERT mRNA and telomerase enzyme activity, and in the cancer lines by alternative lengthening of telomeres (ALT), which rose only minimally in the normal cells.^10,15

In primary human fetal lung fibroblasts that had exhausted their proliferative capacity at passage 34, adding Epithalon re-lengthened telomeres to the size seen at passage 10, and the treated cells completed ten further divisions to passage 44 and were still dividing, while untreated controls had stopped.¹⁶

In female outbred Swiss-derived SHR mice treated from age 3 months until natural death, 54 per group, Epitalon left mean life span, food consumption and body weight unchanged versus saline, but raised the life span of the last 10% of survivors by 13.3% (P<0.01) and maximum life span by 12.3%, cut bone-marrow chromosome aberrations by 17.1% (P<0.05) and lowered leukaemia incidence 6.0-fold; total spontaneous tumour incidence was unchanged.¹⁷

In female FVB/N HER-2/neu transgenic mice treated from age 2 months, the Epitalon arm showed a reduced cumulative number and maximum size of spontaneous mammary tumours versus saline (P<0.05), smaller but not fewer lung metastases, and a 3.7-fold reduction in HER-2/neu mRNA in the tumours; the comparator dipeptide Vilon (Lys-Glu), run in the same experiment, instead increased mammary cancer incidence and shortened tumour latency.¹⁸

In female rats given Ala-Glu-Asp-Gly from age 4 months, life span was unchanged under a standard 12-hour light/dark regimen; only under natural North-West Russian or constant illumination — both of which shortened life on their own — did maximum life span rise, by 95 and 24 days respectively, and spontaneous tumour development was inhibited in the natural-light group alone.¹⁹

In wild-type Canton-S Drosophila melanogaster exposed to epitalon only in the culture medium during the egg-to-larva stage, adult life span rose 11-16% versus untreated flies at concentrations from 0.001x10^-6 to 5x10^-6 wt% of medium for males and 0.01x10^-6 to 0.1x10^-6 wt% for females, with no dose-dependence inside the effective range and effective concentrations 16,000-80,000,000 times lower than those of melatonin.²⁰

In mouse oocytes aged in vitro after ovulation, 0.1 mM Epitalon in the culture medium lowered intracellular reactive oxygen species, reduced the frequency of spindle defects and abnormal cortical granule distribution at 12 and 24 hours, raised mitochondrial membrane potential and mitochondrial DNA copy number, and decreased apoptosis by 24 hours compared with untreated aged oocytes.²¹

In senescent female rhesus monkeys, Epitalon significantly increased evening melatonin production and normalised the circadian rhythm of cortisol secretion measured by immunoenzyme assay, relative to the animals' untreated profile.²²

In perifused pineal glands from young (9-week) and old (27-month) male Wistar rats, Ala-Glu-Asp-Gly at 10^-4 to 10^-6 M had no significant effect on melatonin secretion at either age and did not modify the melatonin rise induced by the beta-adrenergic agonist isoproterenol — a null result co-authored by the peptide's originators, Khavinson and Anisimov.¹³

In a clinical report from the peptide's originating institute, Epitalon therapy in patients with degenerative retinal lesions was said to produce a positive clinical effect in 90% of cases; the paper reports no sample size, comparator arm or outcome definition for the human part, so the figure cannot be interpreted, and the controlled data in the same paper come from Campbell rats, in which the peptide preserved retinal morphological structure and intensified the retina's bioelectric and functional activity.⁵

In the human retinal pigment epithelial line ARPE-19 injured by high glucose — which delayed wound closure, raised reactive oxygen species, lowered antioxidant gene expression and induced epithelial-mesenchymal transition with upregulated fibrosis genes — Epitalon restored the impaired healing and suppressed the hyperglycaemia-induced transition and fibrotic gene expression.²³