Epitalon

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Epitalon
Epitalon.png
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
PubChem CID
UNII
  • InChI=1S/C14H22N4O9/c1-6(15)12(25)17-7(2-3-9(19)20)14(27)18-8(4-10(21)22)13(26)16-5-11(23)24/h6-8H,2-5,15H2,1H3,(H,16,26)(H,17,25)(H,18,27)(H,19,20)(H,21,22)(H,23,24)/t6-,7-,8-/m0/s1
    Key: HGHOBRRUMWJWCU-FXQIFTODSA-N
  • CC(C(=O)NC(CCC(=O)O)C(=O)NC(CC(=O)O)C(=O)NCC(=O)O)N
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).

Epitalon is a synthetic peptide, telomerase activator, and putative anti-aging compound, [1] [2] which was identified as the putative active component of a bovine pineal gland extract known as epithalamin. [3]

Contents

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] though in recent years research using epitalon has started to be conducted elsewhere, focusing mainly on its ability to extend telomere length. [8] [9] [10] [11]

Chemistry

Epitalon is a tetrapeptide with the amino acid sequence Ala-Glu-Asp-Gly and the molecular formula C14H22N4O9. [12]

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. [13]

Epitalon induces decondensation of heterochromatin near the centromeres in cultured lymphocytes originating from samples taken from humans of ages 76 to 80 years. [14]

Epitalon appears to inhibit the synthesis of the MMP9 protein in vitro in aging skin fibroblasts. [15]

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. [16]

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 mice of the C3H/He inbred strain, and is speculated to have oncostatic and anti-metastatic properties. [17]

In a study of chickens subjected to neonatal hypophysectomy and subsequent maturation, epitalon promoted the recovery of the morphological structures of the thymus, [18] as well as the structure and function of the thyroid gland. [19]

Epitalon appears to increase the proliferation of lymphocytes in the thymus, putatively increasing production of interferon gamma by T-cells. [20]

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. [12]

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. [21] [22]

Epitalon and epithalamin appear to restore melatonin secretion by the pineal gland [3] in both aged monkeys and humans. [23]

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. [24]

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. [25]

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. [26] [27]

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. [28] [29]

See also

References

  1. 1 2 Khavinson VK, Bondarev IE, Butyugov AA (June 2003). "Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells". Bulletin of Experimental Biology and Medicine. 135 (6): 590–592. doi:10.1023/a:1025493705728. PMID   12937682. S2CID   7762518.
  2. 1 2 Khavinson VK, Kuznik BI, Tarnovskaia SI, Lin'kova NS (2014). "[Peptides and CCL11 and HMGB1 as molecular markers of aging: literature review and own data]". Advances in Gerontology = Uspekhi Gerontologii. 27 (3): 399–406. PMID   25826983.
  3. 1 2 3 Kozina LS, Arutjunyan AV, Khavinson VK (2007). "Antioxidant properties of geroprotective peptides of the pineal gland". Archives of Gerontology and Geriatrics. 44 Suppl 1: 213–216. doi:10.1016/j.archger.2007.01.029. PMID   17317455.
  4. ↑ Khavinson VK, Lin'kova NS (2012). "[Morphofunctional and molecular bases of pineal gland aging]". Fiziologiia Cheloveka. 38 (1): 119–127. PMID   22567846.
  5. ↑ Anisimov VN, Khavinson VK (2009). "[The use of peptide bioregulators for cancer prevention: results of 35 years of research experience and perspectives]". Voprosy Onkologii. 55 (3): 291–304. PMID   19670728.
  6. ↑ Khavinson VK (2002). "Peptides and Ageing". Neuro Endocrinology Letters. 23 Suppl 3 (3): 11–144. PMID   12374906.
  7. ↑ "Top Management". eng.gerontology.ru. St. Petersburg Institute of Bioregulation and Gerontology. Archived from the original on 2018-01-09. Retrieved 2018-01-08.
  8. ↑ Ullah S, Haider Z, Perera CD, Lee SH, Idrees M, Park S, et al. (February 2025). "Epitalon-activated telomerase enhance bovine oocyte maturation rate and post-thawed embryo development". Life Sciences. 362 123381. doi:10.1016/j.lfs.2025.123381. PMID   39788414.
  9. ↑ Gatta M, Dovizio M, Milillo C, Ruggieri AG, Sallese M, Antonucci I, et al. (August 2025). "The Antioxidant Tetrapeptide Epitalon Enhances Delayed Wound Healing in an in Vitro Model of Diabetic Retinopathy". Stem Cell Reviews and Reports. 21 (6): 1822–1834. doi:10.1007/s12015-025-10911-x. PMC   12356729 . PMID   40493162.
  10. ↑ Al-Dulaimi S, Thomas R, Matta S, Roberts T (September 2025). "Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity". Biogerontology. 26 (5) 178. doi:10.1007/s10522-025-10315-x. PMC   12411320 . PMID   40908429.
  11. ↑ Araj SK, Brzezik J, Mądra-Gackowska K, Szeleszczuk Ł (March 2025). "Overview of Epitalon-Highly Bioactive Pineal Tetrapeptide with Promising Properties". International Journal of Molecular Sciences. 26 (6): 2691. doi: 10.3390/ijms26062691 . PMC   11943447 . PMID   40141333.
  12. 1 2 Vinogradova IA, Bukalev AV, Zabezhinski MA, Semenchenko AV, Khavinson VK, Anisimov VN (December 2007). "Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes". Bulletin of Experimental Biology and Medicine. 144 (6): 825–830. doi:10.1007/s10517-007-0441-z. PMID   18856211. S2CID   930323.
  13. ↑ Khavinson VK, Bondarev IE, Butyugov AA, Smirnova TD (May 2004). "Peptide promotes overcoming of the division limit in human somatic cell". Bulletin of Experimental Biology and Medicine. 137 (5): 503–506. doi:10.1007/s10517-016-3370-x. PMID   15455129. S2CID   13941652.
  14. ↑ Khavinson VK, Lezhava TA, Monaselidze JR, Jokhadze TA, Dvalishvili NA, Bablishvili NK, et al. (October 2003). "Peptide Epitalon activates chromatin at the old age". Neuro Endocrinology Letters. 24 (5): 329–333. PMID   14647006.
  15. ↑ Lin'kova NS, Drobintseva AO, Orlova OA, Kuznetsova EP, Polyakova VO, Kvetnoy IM, et al. (May 2016). "Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro". Bulletin of Experimental Biology and Medicine. 161 (1): 175–178. doi:10.1007/s10517-016-3370-x. PMID   27259496. S2CID   13941652.
  16. ↑ Rosenfeld SV, Togo EF, Mikheev VS, Popovich IG, Khavinson VK, Anisimov VN (March 2002). "Effect of epithalon on the incidence of chromosome aberrations in senescence-accelerated mice". Bulletin of Experimental Biology and Medicine. 133 (3): 274–276. doi:10.1023/a:1015899003974. PMID   12360351. S2CID   26550927.
  17. ↑ 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.
  18. ↑ Pateyk AV, Baranchugova LM, Rusaeva NS, Obydenko VI, Kuznik BI (March 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". Bulletin of Experimental Biology and Medicine. 154 (5): 681–685. doi:10.1007/s10517-013-2029-0. PMID   23658898. S2CID   30171446.
  19. ↑ 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]". Patologicheskaia Fiziologiia I Eksperimental'naia Terapiia. 1 (1): 14–18. PMID   20731122.
  20. ↑ Lin'kova NS, Kuznik BI, Khavinson VK (2012). "[Peptide Ala-Glu-Asp-Gly and interferon gamma: their role in immune response during aging]". Advances in Gerontology = Uspekhi Gerontologii. 25 (3): 478–482. PMID   23289226.
  21. ↑ Khavinson V (2015-07-03). "Peptides, Genome, Aging". khavinson.info. Prof. Vladimir Khavinson. p. 79. Archived from the original on 2018-01-09. Retrieved 2018-01-08.
  22. ↑ Khavinson V (2015-07-03). "Peptides, Genome, Aging". slideshare.net. SlideShare. p. 79. Archived from the original on 2018-01-09. Retrieved 2018-01-08.
  23. ↑ Korkushko OV, Lapin BA, Goncharova ND, Khavinson VK, Shatilo VB, Vengerin AA, et al. (2007). "[Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people]". Advances in Gerontology = Uspekhi Gerontologii. 20 (1): 74–85. PMID   17969590.
  24. ↑ Khavinson V, Razumovsky M, Trofimova S, Grigorian R, Razumovskaya A (August 2002). "Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa". Neuro Endocrinology Letters. 23 (4): 365–368. PMID   12195242.
  25. ↑ Dzhokhadze TA, Buadze TZ, Rubanov KD, Kiriia NA, Lezhava TA (November 2013). "[Genome instability in pulmonary tuberculosis before and after treatment]". Georgian Medical News. 224 (224): 77–81. PMID   24323970.
  26. ↑ Khavinson VK, Morozov VG (2003). "Peptides of pineal gland and thymus prolong human life". Neuro Endocrinology Letters. 24 (3–4): 233–240. PMID   14523363.
  27. ↑ Khavinson VK, Morozov VG (2002). "[Geroprotective effect of thymalin and epithalamin]". Advances in Gerontology = Uspekhi Gerontologii. 10: 74–84. PMID   12577695.
  28. ↑ Korkushko OV, Khavinson VK, Shatilo VB, Antonyk-Sheglova IA (July 2011). "Peptide geroprotector from the pituitary gland inhibits rapid aging of elderly people: results of 15-year follow-up". Bulletin of Experimental Biology and Medicine. 151 (3): 366–369. doi:10.1007/s10517-011-1332-x. PMID   22451889. S2CID   22194443.
  29. ↑ Korkushko OV, Khavinson VK, Shatilo VB, Antonyuk-Shcheglova IA (September 2006). "Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging". Bulletin of Experimental Biology and Medicine. 142 (3): 356–359. doi:10.1007/s10517-006-0365-z. PMID   17426848. S2CID   31963683.
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