Review Article of International Journal of Aging Research
Age-related circadian disturbances in melatonin causing changes in thymus hormones and glucocorticoids rhythmicity in healthy animals and humans
Labunets Irina F.
State Institute of Genetic and Regenerative Medicine National Academy of Medical Sciences of Ukraine, Vyshgorodskaya Street 67, PO Box: 04114 Kiev, Ukraine;
Circadian rhythms of the organism functions cause its adaptation to changes in environmental lighting. The pineal gland is a key regulator of the circadian rhythms of the immune system. The thymus, its central organ, is the source of some hormones, in particular, the highly active thymic serum factor / thymulin. Therefore, the issues of age-related changes in the circadian intra-immune relationships with thymus involvement and the possibility of melatonin influence not only on the above links but also on the glucocorticoids hormones with adaptive effect require an in-depth analysis.
Discussed are the literature data and our own findings how age-related changes in the circadian rhythms of thymus endocrine and adrenal gland glucocorticoid functions are linked with the melatonin-forming function of the pineal gland in healthy animals of different species (mice, rats, rabbits) and humans. The similar manifestations of the above interactions in healthy animals and humans demonstrate the biological significance of the pineal gland for the supporting circadian rhythms of the thymus and adrenal gland functions in the adult organism. The correlation of age-related changes in circadian rhythmicity of pineal gland in healthy animals and human, on the one hand, with the thymus and adrenal glands, on the other hand, has been demonstrated. In addition, the decrease of age-related disorders in the thymulin and glucocorticoid blood levels under the influence of pineal gland factors (melatonin and peptides) was shown. Thus, (a) the thymus endocrine function does not completely disappear in the old organisms and it responds to the effects of melatonin and peptide factors of the pineal gland and (b) age-related pineal gland desynchronosis has pathogenic significance for the formation of circadian disturbances in the thymus hormones and glucocorticoids.
Keywords: melatonin, thymic serum factor/thymulin, glucocorticoids, circadian rhythm, age, animals, humans
How to cite this article:
Labunets Irina F. Age-related circadian disturbances in melatonin causing changes in thymus hormones and glucocorticoids rhythmicity in healthy animals and humans. International Journal of Aging Research, 2018, 1:25. DOI: 10.28933/ijoar-2018-12-0101
1. Bulyk RYe, Herush IV, Pishak VP, Rogovyi YY. Time organization of physiological functions in mammals. General structures involvement.Buk.Med.Herald. 2014; 18(1):144-147. ISSN 1684-7903 (print); ISSN 2413-0737 (online).
2. Reiter RJ, Rosales-Corral S, Coto-Montes A, et al. The photoperiod, circadian regulation and chronodisruption : requisite interplay between the suprachiasmatic nuclei and the pineal and gut melatonin. J. Physiol. Pharmacol. 2011; 62(3): 269-274. PMID 21893686
3. Hardeland R, Cardinali DP, SrinivasanV, et al. Melatonin – a pleiotropic, orchestrating regulator molecule. Prog. Neurobiol. 2011; 93(3):350–384. DOI:10.1016/j.pneurobio.2010.12.004
4. Logan W, Sarkar DK. Circadian nature of immune function. Moll. Cell. Endocrinol. 2012; 349(1): 82–90. DOI:10.1016/j.mce.2011.06.039
5. Labunets I. Pineal gland and rhythms of immune system functions in aging. Experimental study. LAP LAMBERT Academic Publishing: Saarbrucken, 2012. – 133 p ISBN:978-3-659-21567-4
6. Reggiani PC, Schwerdt Ji, Console GM, et al. Physiology and therapeutic potential of the thymic peptide thymulin. Curr Pharm Des. 2014; 20(29): 4690-4696. DOI: 10.2174/1381612820666140130211157
7. Csaba G. The immunoendocrine thymus as a pacemaker of lifespan. Acta Microbiol. Immunol. Hung. 2016; 63(2):139–158. DOI: 10.1556/030.63.2016.2.1
8. Dickmeis Th. Glucocorticoids and the circadian clock. J. Endocrinol. 2009; 200 (1):3–22. DOI:10.1677/JOE-08-0415
9. Linkova NS, Polyakova VO, Kvetnoy IM, et al. Characteristics of pineal gland and thymus relationship at aging. Adv.geront. 2011; 24(1):38–42. ISSN 1561-9125.
10. Goudoshnikov VI. The role of glucocorticoids in aging and age-related pharmacotherapy. Adv. Gerontol. 2011; 24(1):48–53. PMID: 21809620
11. Paltsev MA, Polyakova VO, Kvetnoy IM, et al. Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging. Oncotarget. 2016; 7(11):11972–11983. doi: [10.18632/oncotarget.7863]
12. Mate I, Madrid JA, De la Fuerite M. Chronobiology of the neuroimmunoendocrine system and aging. Curr Pharm Des. 2014; 20(29): 4642-4655. PMID: 24588832
13. Cardinali DP, Esquifino AJ, Srinivasan V., Pandi-Perumal SR. Melatonin and the immune system in aging. Neuroimmunomodulation. 2008;15(4-6):272–278. DOI:10.1159/000156470
14. Mocchegiani E, Santarelli L, TibaldiA, et al. Presence of links between zinc and melatonin during the circadian cycle in old mice: effects on thymic endocrine activity and on the survival. J. Neuroimmunol. 1998; 86(2):111–122. [PMID:9663556]
15. Mc Gillis JP, Hall NR, Goldstein AL. Circadian rhythm of thymosin–α1 in normal and thymectomized mice. J. Immunol. 1983; 131(1):148–151. [PMID:6863916]
16. Labunets IF. Effects of surgical light deprivation on the age-related changes of immune-endocrine interactions in the mice. Lighting regiment, aging and cancer. Proceedings of the conference, Petrozavodsk, 2013, 177-185. ISBN 978-5-906223-44-9
17. Anisimov. VN, Zhukova OV, Labunets, IF, et al. The inhibitory effect of light deprivation on N-nitrosomethylurea-induced carcinogenesis and on the growth of transplanted tumors in rodents-possible involvement of the pineal gland and immune system. Exp. Oncology. 1995; 17 (1):47-54. ISSN 1812-9269.
18. Labunets IF, Butenko GM. The thymus and adaptive changes of the function of the immune system in aging: the role of pineal gland factors. Buk. Med.Herald. 2009;13(4): 186–190. ISSN 1684-7903 (print); ISSN 2413-0737 (online)
19. Molinero P, Soutto M, Benot S, et al. Melatonin is responsible for nocturnal increase observed in serum and thymus of thymosin alpha1 and thymulin concentrations: observations in rats and humans. J. Neuroimmunol. 2000;103(2):180–188.[PMID:10696913]
20. Gubina-Vakulyk GI, Bondarenko LA, Sotnyk NN. Long round-the clock illumination as a factor of accelerated aging of pineal gland. Adv. Gerontol. 2007; 20(1):92–95. ISSN 1561-9125.
21. Labunets IF, Butenko GM, Dragunova VA. et al. Peptide factors of epiphysis and functional rhythms of the thymus and the bone marrow in animals during senescence. Adv.gerontol.=Uspekhi gerontologii. 2004; 13: 81-89 ISSN 1561-9125.
22. Anisimov V.N. Pineal gland, biorhythms and aging of an organism. Usp.Fiziol. Nauk 2008; 39(4):.52-76. ISSN (print) 0301-1798.
23. Labunets IF, Bondarenko LA. Effects of day-and-night lighting on the 24-hour rhythm of thymus endocrine function in rabbits. Lighting regimen, aging and cancer. Proceedings of the conference, Petrozavodsk, 2013, 186-194. ISBN 978-5-906223-44-9
24. Labunets I.F., Bondarenko L.A. Changes in the biorhythms of endocrine function of thymus in rabbits with age in conditions of round-the-clock lighting . Probl.Stareniya I Dolgoletiya. 2015; 24(2):120-128. ISSN 0869-1703
25. Lotosh T.A., Vinogradova I.A., Anisimov V.N. et al Constant lighting as a factor of premature aging. Role of initiation. Lighting regimen, aging and cancer. Proceedings of the conference, Petrozavodsk, 2013, 215-224. ISBN 978-5-906223-44-9
26. Anisimov VN, Vinogradova IA, Panchenko AV, et al. Light-at-night-induced circadian disruption, cancer and aging. Curr Aging Sci. 2012; 5(3):170-177. [PMID:23237593]
27. Bonmati-Carrion MA, Arguelles-Prieto R, Martinez-Madrid MJ, et al. Protecting the melatonin rhythm through circadian healthy light exposure. Int J Mol Sci.2014;15:23448-23500. DOI: 10.3390/ijms151223448
28. Labunets IF, Influence of melatonin on biorhythms of functional status of thymus, immune system and adrenal glands cortex in elderly people. Probl.Stareniya I Dolgoletiya. 2005; 14(4), 313-322 ISSN 0869-1703
29. Korkushko OV, Khavinson VKh, Shatilo VB, Magdich LV, Labunets IF. Circadian rhythms of pineal gland melatonin forming function in healthy elderly people. Adv.gerontol=Uspekhi gerontologii 2004; 15: 70-75 ISSN 1561-9125
30. Labunets IF, Grinevich YuA. Biological rhythms of function of immune system and possibilities of their regulation in patients with malignant tumours (The review of published and authors’ own research data) Clinical oncology. 2014; 2: 46-52. ISSN 2410-2792
31. Labunets IF. Age-related changes in the melatonin and thymulin biorhythms as risk factors for human neurodegenerative diseases. Gerontollogy&Geriatrics Studies. 2017; 1(2). DOI: 10.31031/GGS.2017.01.000506 -5 p.
32. Labunets IF, Butenko GM, Magdich LV et al. Effect of epithalamin on circadian relationship between the endocrine function of the thymus and melatonin-producing function of the pineal gland in elderly people. Bull Exp Biol Med. 2004; 137(5):507-509 [ PMID:15455130]
33. Labunets IF, Rodnichenko AE, Butenko GM. The influence of pineal factors on the bone marrow cell profile in animals of different ages during changes of the thymus functional condition. Adv. Gerontol. 2011; 1(4): 304–309. ISSN 2079-0570 (print), 2079-0589 (online)
34. Labunets I. Immune-Neuroendocrine Interactions Involving Thymus and Pineal Gland in Stem Cell Therapy of Age-Related Diseases. Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (IEMAMC). 2015;15(2):101-120. DOI : 10.2174/1871522215666150831203443
35. Labunets IF. Age-related changes of circadian rhythms of thymic endocrine and glucocorticoid adrenal functions in animals and human: significance of pineal gland factors Clinical and experimental pathology. 2018; 17(3): 162-167 ISSN 1727-4338