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Epithalon Fights Aging by Activating Telomerase

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY. 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.

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Epithalon, also known as Epitalon is a synthetic peptide analog of epithalamin, a protein found in the pineal gland of mammals and of interest for its anti-aging properties. Past research studies have demonstrated that epithalamin can increase maximum life span in animals, decrease levels of free radicals, and alter catalase activity to prevent tissue damage [1]. Epithalamin has been shown to decrease mortality by 52% in fruit flies, by 52% in normal rats, and by 27% in mice prone to certain types of cancer and cardiovascular disease [2].

It has been shown, through extensive animal research, to be a potent regulator of cell metabolism, including growth and cell division. In particular, epithalon is able to extend cell survival in vitro. At least part of the reason that epithalon can extend cell survival comes down to its action on telomeres.

Epithalon has similar effects to epithalamin in mice and rats. It has also shown promise as an anti-cancer agent, reducing spontaneous mammary tumors in mice prone to them and reducing incidence of intestinal tumors in rodents. How does it achieve these effects?

Longevity

Longevity isn't just about living longer, but about living healthier. Studies show that epithalon not only reactivates telomerase and thus extends a cell's life, but that it also reduces rates of DNA mutation, prevents degradation of immune function, promotes the health of the intestinal mucosa, and protects nerves from damage in rodent models [3]-[5]. In other words, epitalon extends both lifespan and health span (the number of years without disease or disability).

Mechanisms of Epithalon

It isn't entirely clear how epithalon produces its wide-ranging effects. It does not influence standard mechanisms of longevity, such as calorie uptake or body weight. It does, however, seem to decrease the frequency of chromosome abberations in mouse models [6], [7]. Epithalon appears to be protective of DNA in more ways than one. It is clear that it activates telomerase and thus prevents the degradation of telomeres (the end caps of DNA strands), but it is less clear how epitalon prevents other types of DNA damage. At least some of the answer lies in its modulation of free radicals, but the mechanism is not sufficient to explain the far-reaching effects of epithalon.

Research into the DNA protecting effects of epithalon is ongoing as are studies in mice regarding the long-term safety of using the peptide. Interestingly, epithalon appears to be more effective in decreasing the effects of aging in rodents. This fact may eventually help to track down the exact mechanisms by which epithalon works.

Telomeres

Telomeres, the repetitive nucleotide sequences at the end of linear chromosomes, protect DNA from degradation and deterioration. A telomere sequence starts out at about 11,000 DNA units (bases) long, but decreases in length to about 4,000 bases in old age. Interestingly, the rate of telomere degradation is faster in men than in women.

Telomeres are like self-sacrificing guards against actual DNA damage. Because they don’t code for anything, telomeres can be sacrificed when DNA is replicated (copied) without actually damaging any genes. This is necessary because DNA replication is an imperfect process. Of course, telomeres eventually get too short to serve their protective role. Cells have mechanisms to detect when this happens. When a telomere becomes too short, the cell either becomes inactive or dies. This is essentially the process of aging at a molecular level.

Epithalon and Telomerase

There is an enzyme, called telomerase reverse transcriptase (telomerase for short), that rebuilds telomeres and thus slows the molecular aging of cells. Unfortunately, telomerase is not 100% effective and thus aging occurs even with this enzyme around.

Research in 1998 demonstrated that artificially boosting telomerase activity could not only extend the lifespan of human somatic (skin) cells in culture, but could actually make them immortal. Since that time, researchers have sought to boost telomerase activity through the use of gene therapy, metabolic suppression, and torpor/hibernation. Each of these approaches has significant drawbacks and none has, as of yet, been demonstrated to have much effect on human aging.

In 2003, the first evidence that epithalon could impact telomerase activity was demonstrated in human somatic cells in vitro. The study found that epithalon could be added to fibroblast cultures that had no detectable telomerase activity to stimulate the production of telomerase. All of the cells demonstrated telomere lengthening1.

Epithalon: Beyond Telomerase

The idea lost traction for a short period, but was revived again in 2016 when research, again using cultured fibroblasts, found that epithalon’s effects extend beyond activation of telomerase. It turns out that epithalon also inhibits the accumulation of senescent proteins like MMP-9. Senescent proteins are those that arise as a result of aging and signal that cells should stop dividing2.

In addition to inhibiting the production of MMP-9, epithalon has been shown to suppress caspase-dependent apoptosis,2. This is one of the main processes by which cells that have short telomeres or other signs of aging are killed.

All of these activities of epithalon are, in some way, connected to its effects on telomere length. That said, it isn’t clear if the above effects are the indirect result of epithalon protecting telomeres or might be a direct result of an as-of-yet-unidentified action of epithalon.

More than Just Anti-Aging

Beyond the fact that epithalon can impact the aging process, its effects on caspase are of interest in several medical conditions. Excessive caspase activity has been identified in neurodegenerative disorders, like Alzheimer’s disease, as well as in numerous autoimmune conditions3,4. A peptide capable of controlling caspase activity may not just slow the aging process, it may prevent or slow the progression of serious neurological and autoimmune diseases.

Resources

[1] V. N. Anisimov, S. V. Mylnikov, T. I. Oparina, and V. K. Khavinson, "Effect of melatonin and pineal peptide preparation epithalamin on life span and free radical oxidation in Drosophila melanogaster," Mech. Ageing Dev., vol. 97, no. 2, pp. 81-91, Aug. 1997.

[2] 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.

[3] S. V. Rosenfeld, E. F. Togo, V. S. Mikheev, I. G. Popovich, V. K. Khavinson, and V. N. Anisimov, "Effect of epithalon on the incidence of chromosome aberrations in senescence-accelerated mice," Bull. Exp. Biol. Med., vol. 133, no. 3, pp. 274-276, Mar. 2002.

[4] V. K. Khavinson, E. G. Rybakina, V. V. Malinin, I. Y. Pivanovich, S. N. Shanin, and E. A. Korneva, "Effects of short peptides on thymocyte blast transformation and signal transduction along the sphingomyelin pathway,"Bull. Exp. Biol. Med., vol. 133, no. 5, pp. 497-499, May 2002.

[5] V. K. Khavinson, N. M. Timofeeva, V. V. Malinin, L. A. Gordova, and A. A. Nikitina, "Effect of vilon and epithalon on activity of enzymes in epithelial and subepithelial layers in small intestine of old rats," Bull. Exp. Biol. Med., vol. 134, no. 6, pp. 562-564, Dec. 2002.

[6] 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, pp. 94-97, Dec. 2013.

[7] V. N. Anisimov, V. K. Khavinson, I. G. Popovich, M. A. Zabezhinski, I. N. Alimova, S. V. Rosenfeld, N. Y. Zavarzina, A. V. Semenchenko, and A. I. Yashin, "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.

[8] Khavinson, V. K., Bondarev, I. E. & Butyugov, A. A. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull. Exp. Biol. Med. 135, 590–592 (2003).

[9] Lin’kova, N. S. et al. Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro. Bull. Exp. Biol. Med. 161, 175–178 (2016).

[10] Goodsell, D. S. The molecular perspective: caspases. The Oncologist 5, 435–436 (2000).

[11] McIlwain, D. R., Berger, T. & Mak, T. W. Caspase functions in cell death and disease. Cold Spring Harb. Perspect. Biol. 5, a008656 (2013).

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