Epithalon

Epithalon, also referred to as Epitalon, Epithalone, or Epithalamin, is a concise synthetic peptide recognized for its ability to activate the telomerase enzyme and trigger melatonin release. Originally formulated in Russia during the 1980s, epithalon has demonstrated its capacity to retard age-related alterations in the reproductive and immune systems and extend the lifespan of mice and rats. While its primary focus lies in anti-aging research, epithalon has also exhibited notable effects in specific cancer types, infectious diseases, and DNA regulation.

Source: PubChem

Sequence: Ala-Glu-Asp-Gly
Molecular Formula: C₁₄H₂₂N₄O₉
Molecular Weight: 390.349 g/mol
PubChem CID: 219042
CAS Number: 307297-39-8

1. The Role of Telomerase in the Anti-Aging Effects of Epithalon

Early experiments involving insects and rodents have demonstrated that epithalon can significantly extend life. In normal and healthy fruit flies and rats, epithalon reduces mortality by 52%. Moreover, in mice susceptible to heart disease and cancer, epithalon increases lifespan by up to 27% compared to control subjects[1]. These remarkable effects of epithalon are attributed, at least in part, to its ability to eliminate harmful free radicals – charged molecules that cause damage to healthy tissues.

Nevertheless, the extension of life by epithalon is not solely dependent on its antioxidant properties. In vitro experiments conducted on human somatic cells provide compelling evidence that epithalon activates an enzyme known as telomerase[2]. Telomerase plays a crucial role in safeguarding telomeres, which are essential for maintaining the health of DNA. By activating telomerase, epithalon directly reduces the number of errors present in DNA strands, thus offering protection against DNA damage[3], [4]. In essence, epithalon shields DNA from accumulating errors over time, a process that can lead to cellular dysfunction, aging, and potentially even cancer in certain cases.

2. Epithalon and DNA Activation

Epithalon’s profound effects on longevity cannot be solely explained by its impact on free radicals or effects on telomeres. Scientists are actively investigating how this short peptide achieves such effects and are delving into the underlying mechanisms. Part of the explanation lies in the fact that epithalon modifies the expression of specific genes.

Studies on cell cultures have revealed that epithalon directly interacts with DNA, leading to the activation and enhancement of certain genes. These genes include CD5, IL-2, MMP2, and Tram1[5]. CD5 and IL-2 influence the immune system’s functionality, while MMP2 plays a crucial role in maintaining the extracellular matrix in the skin, tendons, and other connective tissues. These findings indicate that epithalon may have a significant impact on the immune system and the body’s ability to recover not only from injuries but also from everyday stress.

The immune system’s connection with epithalon is unsurprising, as research in rats has demonstrated that epithalon increases the expression of interferon gamma in aging lymphocytes[6]. Interferon gamma is a vital signaling molecule in the immune system, essential for combating viral infections by activating macrophages, natural killer cells, and T cells.

The following are known DNA interactions of epithalon:

1. CD5 – Leads to immune cell differentiation
2. IL-2 – Increases IL-2 production, which regulates white blood cells
3. MMP2 – Enhances MMP activation and decreases inflammation
4. Tram1 – Enhances protein production
5. Arylalkylamine-N-acetyltransferase – Enhances melatonin production
6. pCREB t – Circadian rhythm regulation and anti-neoplastic effects
7. Telomerase – Telomerase activity increases cell longevity

3. Epithalon and Skin Health

As previously mentioned, epithalon demonstrates a positive impact on the gene regulating MMP2, a protein predominantly present in connective tissues like the skin. Studies conducted on rodents indicate that epithalon not only activates this gene but also stimulates fibroblasts—the cells responsible for producing and maintaining MMP2, collagen, elastin, and other components of the extracellular matrix. Mice exposed to epithalon exhibited a remarkable increase in fibroblast activation, ranging from 30% to 45%[7]. This activation of fibroblasts by epithalon can contribute to accelerated rates of healing and counteract the natural decline in skin structure and integrity associated with aging.

Moreover, epithalon’s beneficial effects on the skin are further supported by its ability to reduce caspase-3 activity. Caspase-3 is an enzyme involved in the apoptosis or programmed cell death pathway. By decreasing caspase-3 activity, epithalon serves to safeguard fibroblasts and other skin cells, prolonging their lifespan and maintaining their health for extended periods[8].

4. Epithalon and Tumor Growth

Researchers have discovered that when administered daily to rats with cancer, epithalon effectively reduces tumor growth[9]. Beyond its tumor-shrinking effects, this peptide also acts as a preventive measure against the metastasis or dissemination of tumors to distant tissues[10], [11]. Currently, there is ongoing investigation into the potential of epithalon as a treatment for Her-2/neu positive breast cancers, and it has also sparked interest in its potential role in inhibiting the development of specific types of leukemia and testicular cancer[12], [13].

Slowed tumor growth in mice exposed to epithalon compared to controls
Source: Wiley Online Library

There is evidence suggesting that epithalon activates the PER1 protein gene, which is present in the hypothalamus. The PER1 protein plays a crucial role in regulating circadian rhythm and is found to be under-expressed in cancer patients. However, it remains unclear whether this under-expression precedes cancer development and contributes to its growth or if it is a consequence of cancer development.

It is evident that the PER1 protein affects cancer growth. Therefore, controlling PER1 expression could potentially serve as a natural method to slow down tumor growth. Research indicates that increased PER1 expression makes cells more sensitive to the effects of radiation. This heightened sensitivity could lead to a reduction in the doses of radiation required to treat certain cancers, offering benefits such as minimizing immediate side effects and reducing the occurrence of secondary tumors following high doses of radiation[14].

PER1 Causes Increased Rates of Ionizing Radiation-Induced Cell Death
Source: Molecular Cell

5. Epithalon and Melatonin Secretion

Melatonin, associated with sleep and aging, is produced by the pineal gland. Studies conducted on rats reveal that epithalon and similar peptides influence both the synthesis and release of melatonin by affecting the expression of two proteins—arylalkylamine-N-acetyltransferase (AANAT) and pCREB transcription protein[15]. Both of these proteins are pivotal in melatonin production and the circadian (day/night) regulation of melatonin release. Additionally, research on monkeys indicates that epithalon has the capability to restore melatonin secretion to normal levels[16].

6. Epithalon and Eyesight

During a trial conducted on rats with retinitis pigmentosa, it was observed that epithalon resulted in improved outcomes for 90% of the subjects[17]. The peptide seems to play a dual role by preserving the normal structure of the eye and enhancing the bioelectric function of the retina, which is essential for maintaining vision.

Epithalon has been found to exhibit minimal side effects and demonstrates both low oral and excellent subcutaneous bioavailability in mice. However, it’s important to note that the dosage per kilogram in mice cannot be directly extrapolated to humans. Therefore, when considering purchasing epithalon from Peptide Shop, it is crucial to understand that it is solely intended for educational and scientific research purposes and not for human consumption. Only licensed researchers should acquire epithalon for their research endeavors.

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

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 renowned for his groundbreaking work in discovering, conducting experimental and clinical studies on novel classes of peptide bioregulators, and pioneering the development of bioregulating peptide therapy. His research focuses on understanding the role of peptides in regulating the mechanisms of aging, and he is particularly involved in the design, pre-clinical, and clinical studies of new peptide geroprotectors.

Over the course of a 40-year-long investigation, Vladimir Khavinson has developed numerous methods of applying peptide bioregulators to slow down the aging process and extend human lifespan. His contributions have led to the introduction of six peptide-based pharmaceuticals and 64 peptide food supplements into clinical practice. Notably, he holds an impressive track record with 196 patents (both Russian and international) and has authored 775 scientific publications.

Two significant books by Vladimir Khavinson, titled “Peptides and Ageing” (NEL, 2002) and “Gerontological aspects of genome peptide regulation” (Karger AG, 2005), present his major achievements and findings in the field.

Furthermore, Vladimir Khavinson played a pivotal role in establishing the scientific specialty “Gerontology and Geriatrics” at the governmental level in the Russian Federation. Under his guidance, an Academic Council has overseen more than 200 Ph.D. and Doctorate theses from various countries.

It is important to clarify that while Prof. Vladimir Khavinson is referenced as one of the leading scientists in the research and development of Epitalon, he is not endorsing or advocating the purchase, sale, or use of this product for any purpose. There is no affiliation or relationship between Peptide Shop and this esteemed doctor. The citation of his work serves solely to acknowledge, recognize, and credit the extensive research efforts conducted by scientists investigating this peptide. References to Prof. Vladimir Khavinson can be found in [1] [2] [5] [6] [7] [9] [12] [13] [15] and [17] under the referenced citations.

1. V. N. Anisimov, S. V. Mylnikov, and V. K. Khavinson, “Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats,” Mech. Ageing Dev., vol. 103, no. 2, pp. 123–132, Jun. 1998. [PubMed]
2. V. K. Khavinson, I. E. Bondarev, and A. A. Butyugov, “Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells,” Bull. Exp. Biol. Med., vol. 135, no. 6, pp. 590–592, Jun. 2003. [PubMed]
3. T. A. Dzhokhadze, T. Z. Buadze, M. N. Gaiozishvili, 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, pp. 94–97, Dec. 2013. [PubMed]
4. V. N. Anisimov et al., “Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice,” Biogerontology, vol. 4, no. 4, pp. 193–202, 2003. [PubMed]
5. V. K. Khavinson, S. I. Tarnovskaya, N. S. Linkova, V. E. Pronyaeva, L. K. Shataeva, and P. P. Yakutseni, “Short cell-penetrating peptides: a model of interactions with gene promoter sites,” Bull. Exp. Biol. Med., vol. 154, no. 3, pp. 403–410, Jan. 2013. [PubMed]
6. N. S. Lin’kova, B. I. Kuznik, and V. K. Khavinson, “[Peptide Ala-Glu-Asp-Gly and interferon gamma: their role in immune response during aging],” Adv. Gerontol. Uspekhi Gerontol., vol. 25, no. 3, pp. 478–482, 2012. [PubMed]
7. 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. [PubMed]
8. N. S. Lin’kova et al., “Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro,” Bull. Exp. Biol. Med., vol. 161, no. 1, pp. 175–178, May 2016. [PubMed]
9. I. A. Vinogradova, A. V. Bukalev, M. A. Zabezhinski, A. V. Semenchenko, V. K. Khavinson, and V. N. Anisimov, “Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes,” Bull. Exp. Biol. Med., vol. 144, no. 6, pp. 825–830, Dec. 2007. [PubMed]
10. G. Kossoy, V. N. Anisimov, H. Ben-Hur, N. Kossoy, and I. Zusman, “Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice,” Vivo Athens Greece, vol. 20, no. 2, pp. 253–257, Apr. 2006. [PubMed]
11. 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, 2002. [PubMed]
12. V. N. Anisimov, V. K. Khavinson, I. N. Alimova, A. V. Semchenko, and A. I. Yashin, “Epithalon 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. [PubMed]
13. I. A. Vinogradova, A. V. Bukalev, M. A. Zabezhinski, A. V. Semenchenko, V. K. Khavinson, and V. N. Anisimov, “Geroprotective effect of ala-glu-asp-gly peptide in male rats exposed to different illumination regimens,” Bull. Exp. Biol. Med., vol. 145, no. 4, pp. 472–477, Apr. 2008. [PubMed]
14. 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. [PubMed]
15. V. K. 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. [PubMed]
16. O. V. 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., vol. 20, no. 1, pp. 74–85, 2007. [PubMed]
17. V. Khavinson, M. Razumovsky, S. Trofimova, R. Grigorian, and A. Razumovskaya, “Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa,” Neuro Endocrinol. Lett., vol. 23, no. 4, pp. 365–368, Aug. 2002. [PubMed]

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