Chemistry:Epitalon

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Short description: Synthetic peptide
Epitalon
Chemical structure of epitalon
Names
IUPAC name
(4S)-4-[[(2S)-2-aminopropanoyl]amino]-5-[[(2S)-3-carboxy-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
Other names
  • Epithalon
  • Epithalone
  • Ala-Glu-Asp-Gly
  • L-Alanyl-L-glutamyl-L-aspartyl-glycine
  • UNII-O65P17785G
Identifiers
3D model (JSmol)
ChemSpider
MeSH C421253
UNII
Properties
C14H22N4O9
Molar mass 390.349
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Epitalon is a synthetic peptide, telomerase activator, and putative anti-aging drug developed by the St. Petersburg Institute of Bioregulation and Gerontology,[1][2] which was identified as the putative active component of a bovine pineal gland extract known as epithalamin.[3]

Most studies on epitalon and epithalamin have been conducted by the St. Petersburg Institute of Bioregulation and Gerontology, primarily overseen by Vladimir Khavinson, in Russia .[2][4][5][6][7]

Chemistry

Epitalon is a tetrapeptide with the amino acid sequence Ala-Glu-Asp-Gly and the molecular formula C14H22N4O9.[8]

Biological effects

Studies in vitro

Epitalon appears to induce telomere elongation via increased telomerase activity in human somatic cells in vitro, based on a study in human fibroblast cell cultures.[1]

Elongation of telomeres by epitalon was sufficient to surpass the Hayflick limit in a cell culture of human fetal fibroblast cells, extending their proliferative potential from termination at the 34th passage in the control cell population to beyond the 44th passage in the treated cell population, while increasing the lengths of their telomeres to levels comparable to those of cells in the original culture.[9]

Epitalon induces decondensation of heterochromatin near the centromeres in cultured lymphocytes originating from samples taken from humans of ages 76 to 80 years.[10]

Epitalon appears to inhibit the synthesis of the MMP9 protein in vitro in aging skin fibroblasts.[11]

Animal studies in vivo

An in vivo study in aging mice found that epitalon treatment significantly reduced the incidence of chromosomal aberrations, both for wild-type mice and for mice characterized by an accelerated aging phenotype, which is consistent with increases in telomere length.[12]

Another study in aging rats found that epitalon increased the activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase.[3]

Epitalon reduced the number of spontaneous tumors and the number of metastases in mice that did develop spontaneous tumors in an experiment on one-year-old female C3H/He mice, and is speculated to have oncostatic and anti-metastatic properties.[13]

In a study of chickens subjected to neonatal hypophysectomy and subsequent maturation, epitalon promoted the recovery of the morphological structures of the thymus,[14] as well as the structure and function of the thyroid gland.[15]

Epitalon appears to increase the proliferation of lymphocytes in the thymus, putatively increasing production of interferon gamma by T-cells.[16]

Another study in aging rats demonstrated extension of life span for rats subjected to constant illumination or to a natural light regimen typical of northern regions.[8]

Human clinical studies

In human clinical studies, epitalon and epithalamin both significantly increased telomere lengths in the blood cells of patients of ages 60-65 and 75-80, and their efficacy was comparable to one another.[17][18]

Epitalon and epithalamin appear to restore melatonin secretion by the pineal gland[3] in both aged monkeys and humans.[19]

A human clinical trial conducted on a sample of retinitis pigmentosa patients found that epitalon produced a positive clinical effect in 90% of cases in the treated group.[20]

In another human clinical trial conducted on a sample of pulmonary tuberculosis patients, epitalon did not appear to correct pre-existing structural aberrations of chromosomes associated with telomere degradation, but did appear to exert a protective effect against the future development of additional chromosomal aberrations.[21]

A human prospective cohort study conducted on a sample of 266 people over age 60 demonstrated that treatment with epithalamin, the pineal gland extract upon which epitalon is based, produced a 1.6–1.8-fold reduction in mortality during the following 6 years, a 2.5-fold reduction in mortality when combined with thymalin, and a 4.1-fold reduction in mortality when combined with thymalin and administered annually instead of only once at study onset.[22][23]

Another prospective cohort study on a sample of 79 coronary patients spanning in excess of 12 years found improved metrics of physical endurance, circadian rhythm, and carbohydrate and lipid metabolism in the treated group relative to the control group following 3 years of biannual epithalamin treatments, as well as a 50% lower rate of cardiovascular mortality, a 50% lower rate of cardiovascular failure and serious respiratory disease, and a 28% lower rate of overall mortality.[24][25]

See also

References

  1. ↑ 1.0 1.1 Khavinson, VKh; Bondarev, IE; Butyugov, AA (2003). "Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells.". Bull Exp Biol Med. 135 (6): 590–592. PMID 12937682. 
  2. ↑ 2.0 2.1 Khavinson, VKh; Kuznik, BI; Tarnovskaia, SI; Lin'kova, NS (2014). "Peptides and CCL11 and HMGB1 as molecular markers of aging: literature review and own data.". Adv Gerontol 27 (3): 399–406. PMID 25826983. 
  3. ↑ 3.0 3.1 3.2 Kozina, LS; Arutjunyan, AV; Khavinson, VKh (2007). "Antioxidant properties of geroprotective peptides of the pineal gland.". Arch Gerontol Geriatr. 44: 213–216. doi:10.1016/j.archger.2007.01.029. PMID 17317455. 
  4. ↑ Khavinson, VKh; Lin'kova, NS (2012). "Morphofunctional and molecular bases of pineal gland aging.". Fizol Cheloveka. 38 (1): 119–127. PMID 22567846. 
  5. ↑ Anisimov, VN; Khavinson, VKh (2009). "The use of peptide bioregulators for cancer prevention: results of 35 years of research experience and perspectives.". Vopr Onkol. 55 (3): 291–304. PMID 19670728. 
  6. ↑ Khavinson, VKh (2002). "Peptides and aging.". Neuro Endocrinol Lett. 23 (3): 11–144. PMID 12374906. 
  7. ↑ "Top Management". St. Petersburg Institute of Bioregulation and Gerontology. http://eng.gerontology.ru/about/top/. 
  8. ↑ 8.0 8.1 Vinogradova, IA; Bukalev, AV; Zabezhinski, MA; Semenchenko, AV; Khavinson, VKh; Anisimov, VN (2007). "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. 144 (6): 825–830. doi:10.1007/s10517-007-0441-z. PMID 18856211. 
  9. ↑ Khavinson, VKh; Bondarev, IE; Butyugov, AA; Smirnova, TD (2004). "Peptide promotes overcoming of the division limit in human somatic cell.". Bull Exp Biol Med. 137 (5): 503–506. doi:10.1007/s10517-016-3370-x. PMID 15455129. 
  10. ↑ Khavinson, VKh; Lezhava, TA; Monaselidze, JR; Jokhadze, TA; Dvalishvili, NA; Bablishvili, NK; Trofimova, SV (2003). "Peptide Epitalon activates chromatin at the old age.". Neuro Endocrinol Lett. 24 (5): 329–333. PMID 14647006. 
  11. ↑ Lin'kova, NS; Drobintseva, AO; Orlova, OA; Kuznetsova, EP; Polyakova, VO; Kvetnoy, IM; Khavinson, VKh (2016). "Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro.". Bull Exp Biol Med. 161 (1): 175–178. doi:10.1007/s10517-016-3370-x. PMID 27259496. 
  12. ↑ Rosenfeld, SV; Togo, EF; Mikheev, VS; Popovich, IG; Khavinson, VKh; Anisimov, VN (2002). "Effect of epithalon on the incidence of chromosome aberrations in senescence-accelerated mice.". Bull Exp Biol Med. 133 (3): 274–276. PMID 12360351. 
  13. ↑ Kossoy, G; Anisimov, VN; Ben-Hur, H; Kossoy, N; Zusman, I (2006). "Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice.". In Vivo. 20 (2): 253–257. PMID 16634527. 
  14. ↑ Pateyk, AV; Baranchugova, LM; Rusaeva, NS; Obydenko, VI; Kuznik, BI (2013). "Effect of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the morphology of the thymus in hypophysectomized young and old birds.". Bull Exp Biol Med. 154 (5): 681–685. doi:10.1007/s10517-013-2029-0. PMID 23658898. 
  15. ↑ Kuznik, BI; Pateiuk, AV; Rusaeva, NS; Baranchugova, LM; Obydenko, VI (2010). "Effects of hypophyseal Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthetic peptides on immunity, hemostasis, morphology and functions of the thyroid gland in neonatally hypophysectomized chicken and one-year-old birds.". Patol Fiziol Eksp Ter. 1: 14–18. PMID 20731122. 
  16. ↑ Lin'kova, NS; Kuznik, BI; Khavinson, VKh (2012). "Peptide Ala-Glu-Asp-Gly and interferon gamma: their role in immune response during aging.". Adv Gerontol. 25 (3): 478–482. PMID 23289226. 
  17. ↑ Khavinson, Vladimir (2015-07-03). "Peptides, Genome, Aging". Prof. Vladimir Khavinson. pp. 79. http://www.khavinson.info/research/peptides-genome-ageing. 
  18. ↑ Khavinson, Vladimir (2015-07-03). "Peptides, Genome, Aging". SlideShare. pp. 79. https://www.slideshare.net/ssuser92681e/peptides-genome-ageing. 
  19. ↑ Korkushko, OV; Lapin, BA; Goncharova, ND; Khavinson, VKh; Shatilo, VB; Vengerin, AA; Antoniuk-Shcheglova, IA; Magdich, LV (2007). "Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people.". Adv Gerontol. 20 (1): 74–85. PMID 17969590. 
  20. ↑ Khavinson, V; Razumovsky, M; Trofimova, S; Grigorian, R; Razumovskaya, A (2002). "Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa.". Neuro Endocrinol Lett. 23 (4): 365–368. PMID 12195242. 
  21. ↑ Dzhokhadze, TA; Buadze, TZh; Rubanov, KD; Kiriia, NA; Lezhava, TA (2013). "Genome instability in pulmonary tuberculosis before and after treatment.". Georgian Med News. 224: 77–81. PMID 24323970. 
  22. ↑ Khavinson, VKh; Morozov, VG (2003). "Peptides of pineal gland and thymus prolong human life.". Neuro Endocrinol Lett. 24 (3): 233–240. PMID 14523363. 
  23. ↑ Khavinson, VKh; Morozov, VG (2002). "Geroprotective effect of thymalin and epithalamin.". Adv Gerontol. 10: 74–84. PMID 12577695. 
  24. ↑ Korkushko, O; Khavinson, VKh; Shatilo, VB; Antonyk-Sheglova, IA (2011). "Geroprotective effect of thymalin and epithalamin.". Adv Gerontol. 10: 74–84. PMID 22451889. 
  25. ↑ Korkushko, OV; Khavinson, VKh; Shatilo, VB; Antonuk-Sheglova, IA (2006). "Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging.". Bull Exp Biol Med. 142 (3): 356–359. doi:10.1007/s10517-006-0365-z. PMID 17426848. 




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