Epithalon Peptide Research: Cellular Aging and Telomere Studies on Epithalon

The tetrapeptide known as epithalon, which is also spelled "epitalon," has the amino acid sequence Ala-Glu-Asp-Gly and the molecular formula C14H22N4O9 in its scientific notation. Epithalon is a synthetic peptide that has been found as the likely active component of epithalamin, which is an extract of bovine pineal glands. It is also a telomerase activator and a putative anti-aging molecule.  The majority of research on Epithalon and Epithalamin has been carried out in Russia by the St. Petersburg Institute of Bioregulation and Gerontology, which is principally directed by Vladimir Khavinson.

Mechanism of Action of  Epithalon Peptide

Epithalon, which has the amino acid sequence Ala-Glu-Asp-Gly, is a synthetic peptide that has been proposed to induce the activation of ribosomal genes, the decondensation of pericentromeric structure heterochromatin, and the release of genes that have been repressed as a result of the age-related condensing of euchromatic chromosome regions. It would appear that Epitahlon stimulates the growth of lymphocytes in the thymus, which in turn stimulates the production of interferon-gamma by T-cells.  Epithalon has been shown to stop the growth of tumors in somatic cells and is effective in preventing the early aging process of cells when tested in vitro.  Many peptides are effective because they disrupt the actions that occur within the cell, and as a result, they eliminate germs.  The synthesis of DNA, RNA, and proteins is inhibited by a number of significant ones.

Research Evidence of  Epithalon Peptide

In both in vitro and in vivo settings, the developmental potential of oocytes declines with the passage of time after ovulation.  Epithalon is a synthetic short peptide that is derived from a natural peptide called epithalamion that is extracted from the pineal gland. It is composed of four amino acids, including glycine, glutamic acid, aspartic acid, and alanine.  There is some evidence that it may give longevity advantages. It is a powerful antioxidant that is comparable to melatonin.  In this particular study, the objective is to investigate whether or not Epithalon has any protective effects on the quality of post-ovulatory aging oocytes.

Epithalon, which is a synthetic derivative of epithalamin, has also been discovered to reduce the incidence of spontaneous cancers in inbred CBA and HER-2/neu transgenic mice, as well as in Swiss-derived SHR mice, and of chemically-induced colon tumors in rats. This was discovered through research conducted in Switzerland.

With the help of Epithalon, the average lifespan of animals that did not have any neoplasms was increased by 34.2% in transgenic FVB/N mice that carried the breast cancer gene HER-2/neu. Additionally, Epithalon slowed down the development of age-related abnormalities in reproductive activity and prevented the formation of neoplasms.  A decrease in the frequency of breast adenocarcinomas, lung metastases, and multiple tumors was observed as a result of the administration of the peptide. Additionally, the number of mice that did not have breast tumors was raised, and the lifespan of mice who had breast tumors was enhanced by 1.4 times in comparison to their control counterparts. 

When compared to the control group, the maximum longevity of outbred Swiss-derived SHR mice was demonstrated to be increased by 12.3% when Epithalon was administered.  The therapy with Epihtalon did not have any effect on the overall incidence of spontaneous tumors; however, it did decrease the development of leukemia by a factor of six in comparison to the group that served as the control sample. 

During the course of the trial, the administration of Epithalon at a daily dose of 1 ýg/rat prevented the growth of tumors in the jejunum and ileum in tumor-bearing LIO rats that were subjected to 1,2-dimethylhydrazine. This resulted in a significant reduction in the number of tumors in the colon when compared to the control group. 

Furthermore, when the medication was administered throughout the trial, Epithalon was able to decrease the mitotic activity of both the epithelial cells that were close to tumors as well as the tumor cells themselves. At the same time, a significant amount of apoptosis was observed in this particular group of rats. 

Melatonin or Epithalon administration was followed by longer mean and maximum survivals in 10% of the final survivors among senescence-accelerated mice (SAM). This observed survival was followed by longer survival times.

Research Applications of Epithalon Peptide

It has been demonstrated that Epithalamin can enhance the generation of melatonin in both aged rats and adults who have pineal gland dysfunction by inducing telomerase activity and telomere elongation. 

It is unclear from the preclinical evidence whether the synthetic Epithalon has activities that are comparable to those of the natural Epithalon with respect to telomere length. 

Even while AEDG peptide was not successful in stimulating melatonin production in rodents, it was found to be effective in increasing melatonin levels in older primates and telomere elongation in human somatic cells. 

The causes for this mismatch are not entirely evident; nevertheless, it is possible that the variances in the test animals or the presence of contaminants in the synthetic tetra-peptide preparation contribute to the enzyme disagreement.

In one clinical experiment for medical sciences, 266 elderly people were given Epithalamin for a period of two to three years, and then they were studied for a period of four to five years after that.  In the abstract, it is said that the treatment "normalize[d] the basic functions of the human organism, i.e. to improve[d] the indices of cardiovascular, endocrine, immune, and nervous systems, as well as homeostasis and metabolism." 

Over the course of three years, seventy elderly individuals, approximately 65 years old, who were diagnosed with "accelerated aging" due to cardiovascular disease were administered epithalamin every six months for a period of three years. The participants were then monitored for a further nine years. 

Treatment consisted of five intramuscular injections of either saline or 10 mg of epithalamin, with intervals of three days between each treatment. 

Epithalamin medication "prevented age-associated impairment of physical endurance, normalized circadian rhythm of melatonin production, and carbohydrate and lipid metabolism," according to a study that followed the treatment group for a period of twelve years and recorded a follow-up rate of twenty-eight percent with the participants. 

A third-party experiment has not been conducted to verify the accuracy of these findings.  Both Epithalamin and Epithalon peptide regulation have been shown to extend the lifetime of flies, mice, and rats, respectively. 

On the other hand, while none of these findings involved Epithalon used in in vitro human cell culture research, a number of putative mechanisms of action that are relevant to Epithalon have been described. When human fetal fibroblasts were treated with Epithalon, the length of their telomeres grew with gene expression and protein synthesis. On the other hand, when cultured leukocytes were treated with Epithalon, chromatin remodeling events occurred, which suggests that epigenetic activities may be taking place. 

Epithalon may also have anti-senescence activity, as evidenced by the fact that treatment of fetal fibroblasts led to cell proliferation that exceeded its Hayflick limit.  On the other hand, there are no publications that independently replicate these results that are not associated with Dr. Khavinson's lab. 

Last but not least, Epithalon might be useful in the case of cancer prevention.  On the basis of a number of preclinical investigations conducted on cancer-prone mice and rats, Epithalon therapy was found to reduce the rates of tumor formation.  

• Safety: Two three-year epithalamin therapy trials, one of which included a follow-up period of twelve years, found no significant side effects in older adults. Preclinical investigations support a positive safety profile; however, in order to validate safety, a well-conducted Phase 1 safety study and independent validation are required. It is particularly challenging to ascertain whether or not the administration of Epithalamin or Epithalon is safe in the absence of data from a phase I safety trial that has been carried out effectively or comprehensive epidemiological data.  Because Epithalamin is a crude polypeptide extract from a cow gland, its overall safety is still up for debate, and it is extremely likely that the manufacturing method will have a significant impact on the safety of the product.  In a similar vein, given that Epithalon is either separated or manufactured synthetically, any impurities could potentially represent a threat to individual safety.  

• The Dosage and the Sources: There have been no clinical trials carried out on Epithalon.  Nevertheless, Epithalamin has been granted approval in Russia for the treatment of symptoms associated with menopause, anovulatory infertility, and malignancies that are dependent on hormones.  In countries other than Russia, it is not authorized for any medicinal applications. Clinical trials that were reviewed used varied doses, delivery, and scheduling, which resulted in a decrease in death rate and a twofold reduction in the risk of mortality specifically related to cardiovascular disease.

Future Research Perspectives of  Epithalon Peptide

Epithalon peptide induces telomerase activity that is of interest in a variety of applications within the field of cellular research, particularly in relation to lifespan, extracellular matrix dynamics, and oxidative stress responses. However, there is still a great deal that needs to be investigated first. 

There have been investigations exploring its implications for cellular aging and regeneration mechanisms as a result of hypotheses surrounding its potential impact on telomerase activity. 

Its potential connections with fibroblasts, the maintenance of the extracellular matrix (ECM), and the modulation of the circadian rhythm all present attractive areas for further investigation in the field of dermatological research. 

Their scientific value is further expanded by the possibility that the peptide has a role in the response to oxidative stress and that it may have an effect on the pathways that connect melatonin. 

Despite the fact that solid findings are still to come, the theoretical qualities of peptide bioregulators continue to pique everyone's interest in the ways in which they could be incorporated into more general questions about the function of cells and their longevity.

References

1. Yue X, Liu SL, Guo JN, Meng TG, Zhang XR, Li HX, Song CY, Wang ZB, Schatten H, Sun QY, Guo XP. Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro. Aging (Albany NY). 2022 Apr 12;14(7):3191-3202. doi: 10.18632/aging.204007. Epub 2022 Apr 12. PMID: 35413689; PMCID: PMC9037278.

2. Donate, FLAFW, Relief, FTW, Art, WTEAN, & Venice, WI (2025). Epithalon Peptides and Skin Cells. Culture .

3. Khavinson, VK, Malinin, VV, Timofeeva, NM, Egorova, VV, & Nikitina, AA (2002). Effects of epithalon on activities of gastrointestinal enzymes in young and old rats. Bulletin of Experimental Biology and Medicine , 133 , 290-292.

4. Khavinson, V., Diomede, F., Mironova, E., Linkova, N., Trofimova, S., Trubiani, O., ... & Sinjari, B. (2020). AEDG Peptide (Epitalon) stimulates gene expression and protein synthesis during neurogenesis: possible epigenetic mechanism. Molecules , 25 (3), 609.