Epitalon, Part II: Mechanism of Action
Peptide bioregulators, like Epitalon, Cortexin or Thymalin work via pleiotropic mechanisms, providing support to diverse areas of day-to-day cellular and tissue-related functions. The culmination of these small supportive mechanisms is believed to produce the purported anti-ageing effect of peptide bioregulators and, in particular, Epitalon. In this article, a few central mechanisms contributing to this preserving effect will be highlighted.
Physiology
To begin, peptides are small chains of amino acids (the basic units of organic matter) linked by amide bonds, & can be thought of as «small proteins». Proteins are larger macromolecules comprised of many more amino acids linked together. Despite their size, however, peptides play many important roles in the normal functioning of the human body. Some examples include insulin, which is responsible for controlling levels of glucose within the blood, and substance P, a peptide playing a major role in the perception of pain.
Telomere Elongation
With each cellular replication, the telomeres (in green) are shortened. The maximum number of times that DNAcan be replicated is called the Hayflick Limit. Once this number is reached, the cell undergoes apoptosis or programmed cell death. Telomerase is an enzyme which restores telomere length.
Epitalon is a synthetic peptide which were originally developed based upon the action of epithalamin, a hormone produced by the pineal gland. This hormone was found to stimulate the production of telomerase, an enzyme which plays a role in maintaining telomere length. Telomeres are non-coding terminal regions of DNA strands which preserve the integrity of the strand. With each revision, telomeres are shortened until the DNAstrand cannot be further replicated. This process is highly implicated in the ageing process. Elongating telomeres theoretically extend the lifespan of a copy of DNA and allows it to replicate more times than usual. This was the theory behind the development of Epitalon®, a synthetic version of epithalamin which also stimulates the production of telomerase. Indeed, this theory has been confirmed in vitro in human cell cultures[1].
Neutralisation of Harmful Free Radicals
The role of antioxidants in mitigating damage from free radicals.
Cytotoxicity secondary to free radical damage has been implicated in the ageing process[2]. Administration of epithalon has also been shown to exert an antioxidant effect[3]. The presence of toxic compounds within the body can lead to the formation of reactive oxygen species (ROS) which can damage DNA, leading to cellular death &/or mutations leading to the formation of cancerous cells.
Inhibition of Cancer Formation & Growth
Maintaining the integrity of the genetic information stored in DNA is one of the mechanisms in which peptide bioregulators work to prevent cancer.
The anti-carcinogenic effect of Epitalon has also been explored in several animal studies. Epitalon has shown beneficial effects in animal models of breast[4] & colorectal cancer[5] without significant rates of adverse effects. Purported mechanisms include inhibition of carcinogenic receptor expression (Human Epithelial growth factor Receptor 2, also known as HER2, which is over-expressed in breast cancer) & retardation of metastasis[6],[7].
Attenuation of Inflammation
Inflammation is a normal immune response that can become dysregulated and potentiated in a broad spectrum of disorders from rheumatoid arthritis to ulcerative colitis and even has been implicated in psychiatric disorders. The inflammatory process is dependent upon intercellular communication mediated by biomolecules such as cytokines, C-reactive protein, and other acute phase reactants[8]. Epithalamin has been observed to play a role in the regulation of these molecules[9] & thus attenuate the inflammatory response[10].
Endocrine Regulation
Hormones released by endocrine glands play signalling roles that coordinate different organs of the body.
Epitalon has been shown to help regulate endocrine activity in the body. Hormones are responsible for many key signalling circuits between cells which on a larger scale comprise the functions of large organs. For example, melatonin is a hormone which regulates the circadian rhythm, an internal biological clock. Endogenous melatonin production has been observed to decrease with ageing. A 2007 study of Epitalon administration in elderly patients found that the compound helped to restore pineal gland function & increased release of melatonin[11], which is purported to be the mechanism behind the restoration of sleep. Other studies have found that Epitalon exerts regulatory effects on gonadotropic hormones (FSG, LG, prolactin), which are involved in sexual & reproductive functions[12].
Summary
These are but a few of the many mechanisms by which Epitalon support normal functioning of the human body, and ultimately produce their anti-ageing effect. Telomerase activation, neutralisation of free radicals, oncostasis, modulation of inflammatory mediators, and endocrine regulation are all ways in which peptide bioregulators can help to ultimately prolong life. Peptide bioregulators as a class are still relatively uncharacterised, and most of the available clinical data are from Russian studies. As interest in this class of drugs grows, more mechanisms of action may be discovered, and the true treatment effects of Epitalon and peptide bioregulators may begin to be better understood.
References
1. ↑ Khavinson VK, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity & telomere elongation in human somatic cells. Bull Exp Biol Med. 2003 Jun;135(6):590-2.
2. ↑ Hekimi S, Lapointe J, Wen Y. Taking a “good” look at free radicals in the aging process. Trends In Cell Biology. 2011;21(10) 569-76.
3. ↑ Anisimov VN, Arutjunyan AV, Khavinson VK. Effects of pineal peptide preparation Epithalamin on free-radical processes in humans and animals. Neuro Endocrinol Lett. 2001;22(1):9-18.
4. ↑ Anisimov VN, Khavinson VK, Provinciali M, Alimova IN, Baturin DA, Popovich IG, et al. Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumours in HER-2/neu transgenic mice. Int J Cancer. 2002 Sep 1;101(1):7-10.
5. ↑ Anisimov VN, Khavinson VK, Popovich IG, Zabezhinski MA. Inhibitory effect of peptide Epitalon on colon carcinogenesis induced by 1,2-dimethylhydrazine in rats. Cancer Lett. 2002 Sep 8;183(1):1-8.
6. ↑ Kossoy G, Zandbank J, Tendler E, Anisimov V, Khavinson V, Popovich I, et al. Epitalon and colon carcinogenesis in rats: proliferative activity & apoptosis in colon tumors & mucosa. Int J Mol Med. 2003 Oct;12(4):473-7.
7. ↑ Kossoy G, Anisimov VN, Ben-Hur H, Kossoy N, Zusman I. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo. 2006 Mar-Apr;20(2):253-7.
8. ↑ Owen JA, Punt J, Stranford SA. Immunology. 7th ed. New York: W.H. Freeman & Company; (c) 2013.
9. ↑ Labunets IF, Butenko GM, Korkushko OV, Shatilo VB. Effect of epithalamin on the rhythm of immune and endocrine systems functioning in patients with chronic coronary disease. Bull Exp Biol Med. 2007 Apr;143(4):472-5.
10. ↑ Khavinson VKh. Peptide regulation of aging. Proceedings of the 17th World Congress of the International Association of Gerontology; Jul 1–6 2001; Vancouver, Canada. Gerontology: 2001; 47(1).
11. ↑ Korkushko OV, Lapin BA, Goncharova ND, Khavinson VK, Shatilo VB, Vengerin AA, et al. Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys & elderly people. Adv Gerontol. 2007;20(1):74-85.
12. ↑ Slepushkin VD, Mordovin VF, Zoloev GK, Iakovleva RA, Khavinson VK. Effect of the epiphysial preparation epithalamin on the gonadotropic function of the hypophysis. Probl Endokrinol (Mosk). 1983 Nov-Dec;29(6):51-4.