Key findings
- Added to telomerase-negative human fetal fibroblast culture the peptide induced expression of the telomerase catalytic subunit, enzymatic activity of the telomerase and elongation of telomeres. [1]
- A later study across normal epithelial and fibroblast cells and two breast cancer lines reported concentration dependent telomere extension, through hTERT and telomerase upregulation in the normal cells and through alternative lengthening of telomeres in the cancer lines. [2]
- Mass spectrometry and HPLC of the pineal polypeptide complex resolved its peptide length distribution and detected this tetrapeptide among the tetrapeptide fraction by selective reaction monitoring. [3]
- In human gingival mesenchymal stem cells the peptide raised four neurogenic differentiation markers at both mRNA and protein level, and molecular modelling placed its preferred binding at two named sites of histones H1/3 and H1/6 that contact DNA. [4]
Identity and structure
- Origin
- Constructed from the amino acid analysis of the pineal polypeptide complex, and later detected within the tetrapeptide fraction of that same complex [3]
- Complex composition in cited work
- The pineal polypeptide complex it was found in contained 3.26 percent free amino acids, 23.19 percent dipeptides, 50.72 percent tripeptides, 22.10 percent tetrapeptides and 0.72 percent pentapeptides [3]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
The telomere result is described at the level of gene reactivation rather than of direct enzyme binding. Expression of the telomerase catalytic subunit, telomerase activity and telomere length all rose together in a culture that had none of the three beforehand, which the authors attribute to reactivation of the telomerase gene in a somatic cell. [1]
A later replication separates two routes to the same endpoint. Normal cells extended telomeres through hTERT messenger RNA and telomerase activity while the cancer lines did so through alternative lengthening of telomeres, with only a minor alternative lengthening signal in the normal cells. [2]
Two lines of work place the tetrapeptide on chromatin rather than at a receptor. Labelled peptide entered the nucleus and nucleolus of HeLa cells and bound oligonucleotides with a sequence and methylation dependent preference, and molecular modelling of the unlabelled peptide favours binding at two DNA-contacting sites of linker histones. [6][4]
Research findings
In vitro
- System
- Telomerase-negative human fetal fibroblast culture
- Measured
- Expression of the telomerase catalytic subunit, telomerase enzymatic activity and telomere length
- Reported
- All three rose after addition of the peptide, which the authors read as reactivation of the telomerase gene in a somatic cell. [1]
In vitro
- System
- Normal epithelial cells and fibroblasts alongside the 21NT and BT474 breast cancer lines
- Measured
- Telomere length, hTERT messenger RNA expression, telomerase enzyme activity and alternative lengthening of telomeres activity, by quantitative PCR and immunofluorescence across a concentration range
- Reported
- Telomere length increased with concentration in the normal cells through hTERT and telomerase upregulation. The cancer lines also extended telomeres but through alternative lengthening of telomeres, and that route showed only a minor increase in the normal cells, so the authors report it as specific to the cancer lines. [2]
Analytical
- System
- The polypeptide complex of the epiphysis, fractionated and analysed rather than the synthetic peptide
- Measured
- Distribution of free amino acids and of di-, tri-, tetra- and pentapeptides by mass spectrometry and HPLC, and detection of this specific tetrapeptide by selective reaction monitoring
- Reported
- The complex contained 3.26 percent free amino acids, 23.19 percent dipeptides, 50.72 percent tripeptides, 22.10 percent tetrapeptides and 0.72 percent pentapeptides, and this tetrapeptide was detected among the tetrapeptide fraction. [3]
In vitro
- System
- Human gingival mesenchymal stem cells, with a parallel molecular modelling arm against linker histones
- Measured
- Protein synthesis and messenger RNA expression of the neurogenic differentiation markers Nestin, GAP43, beta Tubulin III and Doublecortin, and predicted binding sites on histones H1/3 and H1/6
- Reported
- All four markers increased in protein, and their messenger RNA rose by 1.6 to 1.8 times. Modelling favoured binding at the His-Pro-Ser-Tyr-Met-Ala-His-Pro-Ala-Arg-Lys and Tyr-Arg-Lys-Thr-Gln sites of the two linker histones, which the authors propose as a route to the transcription change. [4]
In vitro
- System
- HeLa cells incubated with a fluorescein isothiocyanate labelled conjugate of the peptide, so cell entry was followed with a labelled analogue, alongside pinealon and testagen
- Measured
- Fluorescence in cytoplasm, nucleus and nucleolus, and Stern-Volmer quenching constants against labelled single-stranded and double-stranded deoxyribooligonucleotides and DNA ethidium bromide complexes
- Reported
- Labelled peptide fluorescence appeared in cytoplasm, nucleus and nucleolus. Quenching constants varied with peptide primary structure, and this tetrapeptide bound preferentially to CNG containing and CAG containing sequences while discriminating the cytosine methylation state of the target. [6]
In vitro
- System
- Human periodontal ligament stem cells and human gingival mesenchymal stem cells at the 25th passage, with the Lys-Glu-Asp peptide tested alongside rather than this peptide alone
- Measured
- Expression of the senescence markers p16 and p21 by RT-PCR, confirmed by immunofluorescence, against an untreated control group
- Reported
- This tetrapeptide lowered p16 and p21 messenger RNA by 1.56 to 2.44 times relative to control and the comparison peptide lowered them by 1.82 to 3.23 times, with the immunofluorescence agreeing. [7]
In vitro
- System
- Mouse oocytes cultured after ovulation and assessed at 6, 12 and 24 hours
- Measured
- Intracellular reactive oxygen species, spindle defects, cortical granule distribution, mitochondrial membrane potential, mitochondrial DNA copy number and apoptosis
- Reported
- Reactive oxygen species fell at 0.1 mM. Spindle defects and abnormal cortical granule distribution decreased at 12 and 24 hours, mitochondrial membrane potential and mitochondrial DNA copy number rose, and apoptosis was lower by 24 hours. [5]
Handling for in-vitro work
Open questions
- The 2003 report is brief and the authors extend a culture observation to an inference about lifespan that its measurements do not test.
- Telomere extension occurred by two different routes depending on cell type in the cited replication, and the cited work does not establish which route a given preparation would engage.
- Histone binding is a modelling result and the oligonucleotide preference comes from fluorescence quenching constants, so no solved structure of the peptide on chromatin appears in the cited set.
- Several cited studies test this tetrapeptide beside related short peptides, so effects specific to this sequence are separable only where the authors report them separately.
A clinical literature on pineal peptide preparations exists and concerns finished formulations; it is out of scope for a research material profile.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
- RV-24-0043-1 ↗Epitalon · 99.40% HPLC2026-09-16
References
- Khavinson VKh, Bondarev IE, Butyugov AA Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bulletin of experimental biology and medicine. 2003.
- Al-Dulaimi S, Thomas R, Matta S, et al. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology. 2025.
- Khavinson VK, Kopylov AT, Vaskovsky BV, et al. Identification of Peptide AEDG in the Polypeptide Complex of the Pineal Gland. Bulletin of experimental biology and medicine. 2017.
- Khavinson V, Diomede F, Mironova E, et al. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism. Molecules (Basel, Switzerland). 2020.
- Yue X, Liu SL, Guo JN, et al. Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro. Aging. 2022.
- Fedoreyeva LI, Kireev II, Khavinson VKh, et al. Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA. Biochemistry. Biokhimiia. 2011.
- Sinjari B, Diomede F, Khavinson V, et al. Short Peptides Protect Oral Stem Cells from Ageing. Stem cell reviews and reports. 2020.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.