Epithalon

Epitalon Research Formula

Until very recently, Sub-Q administration has been the most common means of administering peptides. This is because peptides are easily degraded by enzymes in the gastrointestinal tract, do not cross GI cell membranes all that well, and are generally too large for transporters in the digestive tract to deal with. As it stands, most peptides have an oral bioavailability of less than 1%.

Over the last several decades, however, scientists have developed an arsenal of tools that help to make peptides more orally bioavailable. These tools are not only aimed at the delivery of peptides for medicinal purposes, but to ease administration during research as well. After all, it is easier to administer oral peptides to most mammals than it is to administer an injection. With appropriate formulation, some peptides can now even be administered with food or water. The tools that make this possible include

• Chemical modification
• Mucoadhesive polymeric systems
• Co-administration of enzyme inhibitors
• Co-administration of absorption enhancers
• Formulation vehicles, and:
  • Emulsions
  • Microspheres
  • Nanoparticles
  • Liposomes

Formulation vehicles are proving to be a highly beneficial option because they provide multiple protections at once. Microencapsulation, for instance, protects the peptides from enzymatic degradation and boosts absorption by bypassing the need for transporters. As such, multiple peptides that were once considered to only be administrable via injection, like insulin, are now being developed for oral administration. As a result of these advances, the oral bioavailability of peptides has increased from less than 1% in most cases to as high as 50% in some situations.

Epitalon has one advantage in that it is an exceptionally small peptide. This allows much of it to be packaged easily into a micro-encapsulated vehicle. This also makes it easier for the peptide to penetrate cell membranes and to penetrate the blood-brain barrier once it is absorbed. Additionally, Epitalon has no tertiary structure because it is so small. This means that enzymatic degradation is less of a problem. All these features combined to make Epitalon an excellent candidate for oral research administration using these new techniques.

Epitalon Structure

Amino Acid Sequence: Ala-Glu-Asp-Gly (AEDG)
Molecular Formula: C₁₄H₂₂N₄O₉
Molecular Weight: 390.349 g/mol
PubChem CID: 219042
CAS Number: 307297-39-8
Synonyms: Epithalon, Epithalone, Epithalamin, Epithalamine, AEDG

Source: PubChem

Epitalon Research Benefits

An oral form of Epitalon is sought after because making it easier to administer Epitalon will open whole new branches of research. The peptide has been under active investigation for nearly 50 years, mostly because of its well-known effects on DNA activity. Epitalon is helping scientists to better understand how to turn specific genes or regions of DNA on and off. Having specific control of gene activation could eventually be used to make us stronger, smarter, more resistant to disease, or even extend our lives. Epitalon offers tantalizing evidence about how we can learn more about the control of DNA expression. Thus, having an easy-to-administer oral formulation is fundamental to extending Epitalon research efforts and hastening the rate of discovery.

What Does Epitalon Do?

Epitalon has long been understood to preserve telomeres, which are the protective end caps found on fragments of mammalian DNA (chromosomes). Telomeres protect DNA from degradation as it is replicated during cell division (one cell splitting into two). Telomeres themselves suffer degradation, however, and eventually become too short to be effective. At this point, a cell will either commit cell suicide in a process called apoptosis or it will go dormant in a process called senescence. Both processes lead to tissue aging and eventual dysfunction. Senescence is one of the primary drivers of aging.

Epitalon has been shown to activate an enzyme called telomerase, which repairs telomeres. More active telomerase generally means that cells age more slowly and remain functional for longer. The net result is that overall aging appears to be slowed down. Research in rodents indicates that Epitalon may extend life by as much as 27% via this mechanism[2], [3].

As it turns out, Epitalon does not only activate telomerase. As noted above, Epitalon has been shown to affect expression for several genes through alteration of DNA structure. This process, called epigenetic modification, is of intense interest to scientists because it provides the foundation for controlling gene expression at a very fine level. If we someday learn how to harness epigenetic technology, humanity could potentially alter everything from an individual’s eye color to how intelligent a person is or how long someone lives. Here is a look at some of the known genes that Epitalon influences.

Known Effects of Epitalon

Immune System

Epitalon interacts with at least a half of a dozen genes involved in the function of the immune system. By altering CD5 expression, Epitalon can enhance differentiation of cells in the immune system. By regulating IL-2, Epitalon adjusts white blood cell production.

Skin

Epitalon changes the expression of MMP2 and Tram1, both of which are important to the health of skin. MMP2 is critical to the maintenance of thinks like collagen and elastin, which are critical components of skin, tendons, muscle, and more. Tram1 is a general regulator of protein production and helps to increase how much protein is produced by cells during growth, wound repair, or as a response to exercise. Mice exposed to Epitalon have 30-45% more fibroblast activity[4]. Fibroblasts are the cells the produce extracellular matrix.

Neurological System

Cutting edge research (carried by the father of modern peptide synthesis, Professor Vladimir Khavinson), indicates that Epitalon stimulates the growth of neurons. Dr. Khavinson’s work shows that Epitalon increases the production of nestin, GAP43, Beta Tubulin III, and Doublecortin in cells derived from the lining of the mouth. Each of these peptides is a marker of neuron differentiation, suggesting that Epitalon alters gene expression in a way that favors the development of nerve cells[5], [6].

The eyes, which are an extension of the neurological system, are also impacted by Epitalon. Research shows that the peptide may help to preserve the normal structure of the eye and boost bioelectric functions in the retina that are critical for sight[7].

Cancer

When Epitalon is given to rats with cancer, tumor growth slows and rates of metastasis (spread of cancer) decrease. There is current research into whether Epitalon can slow or prevent the growth of Her-2/Neu positive breast cancers. It is thought that these beneficial effects are mediated through Epitalon’s activation of PER1, which is under-expressed in cancer[8], [9].

Circadian Rhythm

Epitalon’s regulation of PER1 is not only important in cancer but may also affect circadian rhythm (sleep-wake cycles) in mammals. There is some interest in whether PER1 activation might help to protect against jet lag, the detrimental effects of shift work, and other sleep disorders[10].

Research in rats shows that Epitalon affects melatonin production and release. In monkeys, Epitalon is able to restore normal melatonin secretion following injury[11], [12]. This has wide-ranging potential applications in stroke, traumatic brain injury, PTSD, and more.

Epitalon (Oral) Summary

Epitalon has several beneficial properties but is limited to some extent in research settings by the need to administer it via injection. The development of an orally bioavailable form of Epitalon would not only open the door to future development as a pharmaceutical agent, but it would also enhance the current rate at which research can be conducted. It would also expand the areas of application for Epitalon. The development of orally bioavailable peptides is a necessary step in the continuing evolution of peptide sciences, with Epitalon being just one of many orally bioavailable peptides to come.

Article Author

The above literature was researched, edited and organized by Dr. E. Logan, M.D. Dr. E. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Scientific Journal Author

Vladimir Khavinson is a Professor, President of the European region of the International Association of Gerontology and Geriatrics; Member of the Russian and Ukrainian Academies of Medical Sciences; Main gerontologist of the Health Committee of the Government of Saint Petersburg, Russia; Director of the Saint Petersburg Institute of Bioregulation and Gerontology; Vice-president of Gerontological Society of the Russian Academy of Sciences; Head of the Chair of Gerontology and Geriatrics of the North-Western State Medical University, St-Petersburg; Colonel of medical service (USSR, Russia), retired. Vladimir Khavinson is known for the discovery, experimental and clinical studies of new classes of peptide bioregulators as well as for the development of bioregulating peptide therapy. He is engaged in studying of the role of peptides in regulation of the mechanisms of ageing. His main field of actions is design, pre-clinical and clinical studies of new peptide geroprotectors. A 40-year-long investigation resulted in a multitude of methods of application of peptide bioregulators to slow down the process of ageing and increase human life span. Six peptide-based pharmaceuticals and 64 peptide food supplements have been introduced into clinical practice by V. Khavinson. He is an author of 196 patents (Russian and international) as well as of 775 scientific publications. His major achievements are presented in two books: “Peptides and Ageing” (NEL, 2002) and “Gerontological aspects of genome peptide regulation” (Karger AG, 2005). Vladimir Khavinson introduced scientific specialty “Gerontology and Geriatrics” in the Russian Federation on the governmental level. Academic Council headed by V. Khavinson has oversighted over 200 Ph.D. and Doctorate theses from many different countries.

Prof. Vladimir Khavinson is being referenced as one of the leading scientists involved in the research and development of Epitalon. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Peptide Sciences and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide.

Referenced Citations

1. J. Shaji and V. Patole, “Protein and Peptide Drug Delivery: Oral Approaches,” Indian J. Pharm. Sci., vol. 70, no. 3, pp. 269–277, 2008, doi: 10.4103/0250-474X.42967.
2. V. Kh. Khavinson, I. E. Bondarev, and A. A. Butyugov, “Epitalon Peptide Induces Telomerase Activity and Telomere Elongation in Human Somatic Cells,” Bull. Exp. Biol. Med., vol. 135, no. 6, Art. no. 6, Jun. 2003, doi: 10.1023/A:1025493705728.
3. T. A. Dzhokhadze, T. Z. Buadze, M. N. Gaĭozishvili, M. A. Rogava, and T. A. Lazhava, “[Functional regulation of genome with peptide bioregulators by hypertrophic cardiomyopathy (by patients and relatives)],” Georgian Med. News, no. 225, Art. no. 225, Dec. 2013.
4. N. I. Chalisova, N. S. Lin’kova, A. N. Zhekalov, A. O. Orlova, G. A. Ryzhak, and V. K. Khavinson, “[Short peptides stimulate skin cell regeneration during ageing],” Adv. Gerontol. Uspekhi Gerontol., vol. 27, no. 4, pp. 699–703, 2014.
5. V. Khavinson et al., “AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism,” Mol. Basel Switz., vol. 25, no. 3, p. E609, Jan. 2020, doi: 10.3390/molecules25030609.
6. T. D. Brown, K. A. Whitehead, and S. Mitragotri, “Materials for oral delivery of proteins and peptides,” Nat. Rev. Mater., vol. 5, no. 2, Art. no. 2, Feb. 2020, doi: 10.1038/s41578-019-0156-6.
7. “Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa. – NeL.edu.” https://www.nel.edu/pineal-regulating-tetrapeptide-epitalon-improves-eye-retina-condition-in-retinitis-pigmentosa-2210/ (accessed Nov. 15, 2022).
8. V. N. Anisimov et al., “Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice,” Int. J. Cancer, vol. 101, no. 1, pp. 7–10, Sep. 2002, doi: 10.1002/ijc.10570.
9. V. N. Anisimov, V. K. Khavinson, I. N. Alimova, A. V. Semchenko, and A. I. Yashin, “Epitalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice,” Bull. Exp. Biol. Med., vol. 134, no. 2, pp. 187–190, Aug. 2002, doi: 10.1023/a:1021104819170.
10. S. Gery, N. Komatsu, L. Baldjyan, A. Yu, D. Koo, and H. P. Koeffler, “The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells,” Mol. Cell, vol. 22, no. 3, pp. 375–382, May 2006, doi: 10.1016/j.molcel.2006.03.038.
11. V. Kh. Khavinson, L. K. Shataeva, and A. A. Chernova, “Effect of Regulatory Peptides on Gene Transcription,” Bull. Exp. Biol. Med., vol. 136, no. 3, pp. 288–290, Sep. 2003, doi: 10.1023/B:BEBM.0000008986.02891.de.
12. O. Korkushko et al., “[Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people],” Adv. Gerontol. Uspekhi Gerontol. Ross. Akad. Nauk Gerontol. Obshchestvo, vol. 20, pp. 74–85, Feb. 2007.

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The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body.  These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease.  Bodily introduction of any kind into humans or animals is strictly forbidden by law.