ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМП10.25789/YMJ.2020.72.27ymj-738Research ArticleНАУЧНЫЕ ОБЗОРЫ И ЛЕКЦИИSCIENTIFIC REVIEWS AND LECTURESГенетические аспекты регуляции циркадных ритмов, влияющих на устойчивость к стрессуGenetic aspects of regulation of circadian rhythms as a factor in stress resistanceСоловьеваН. А.SolovievaN. A.

Соловьева Наталья Алексеевна – к.м.н., с.н.с.

Solovieva Natalya Alekseevna - candidate of medical sciences, senior researcher of the Institute for Biological Problems of Cryolithozone

sonata608@yandex.ruКолосоваО. Н.KolosovaO. N.

Колосова Ольга Николаевна – д.б.н., проф., гл.н.с.

Kolosova Olga Nikolaevna - Doctor of Biological Sciences, Professor, Chief Researcher of the Institute for Biological Problems of Cryolithozone

Институт биологических проблем криолитозоны ФИЦ ЯНЦ СО РАНРоссияFederal Research Center of YSC SB RASRussian Federation20200206202504112115Copyright © Соловьева Н.А., Колосова О.Н., 20252025Соловьева Н.А., Колосова О.Н.Solovieva N.A., Kolosova O.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/738

В статье представлены результаты анализа литературных данных, посвященных молекулярно-генетическим механизмам контроля и регуляции циркадных ритмов, определяющих хронотип человека.Установлено, что нарушение циркадных ритмов может приводить к снижению устойчивости организма к воздействию стрессорных факторов с последующим развитием процессов дезадаптации, что в свою очередь может быть пусковым механизмом начала развития заболеваний.Известно, что молекулярно-генетический контроль циркадных ритмов состоит из взаимодействующих положительных и отрицатель-ных обратных связей регулирующих петель «часовых» генов, таких как Bmal1, Clock, Per1, Per2, Per3, TIM, Npas2, Cry1 и Cry2, Csnk1d, Csnk1e, Rev-erbα, Rora, Bhlhe40, Bhlhe41, а также генов FBXL3, FTO, MADD, CYP2A6, ARNTL, Mel1a, Mel1b и GPR50 и др. Несмотря на то, что основные составляющие молекулярно-генетических механизмов циркадных ритмов уже установлены, вопрос регуляции их работы и взаимодействия между собой остается актуальным.Таким образом, понимание молекулярных механизмов и определение генетических маркеров, вызывающих нарушение циркадных ритмов, является важным этапом для разработки методов, направленных на профилактику и коррекцию патологических состояний, обусловленных процессами дезадаптации.

The article presents the results of the analysis of the literature data on the molecular genetic mechanisms of control and regulation of circadian rhythms that determine the chronotype of a person.It has been established that disturbance of circadian rhythms arising as a result of psychoemotional and physical stress expressed in degree and / or duration, can lead to a decrease in the body's resistance to stress factors with the subsequent development of maladjustment processes, which in turn can be a trigger mechanism for the onset of the development of such pathological conditions as diseases of the cardiovascular system, gastrointestinal tract, autoimmune, mental, neurodegenerative, oncological and other diseases.According to the results of numerous studies, the molecular genetic control of circadian rhythms consists of interacting positive and negative feedbacks of regulatory loops of clock genes, such as genes Bmal1, Clock, Per1, Per2, Per3, TIM, Npas2, Cry1 and Cry2, Csnk1d, Csnk1e, Rev-erbα, Rora, Bhlhe40, Bhlhe41, as well as genes FBXL3, FTO, MADD, CYP2A6, ARNTL, Mel1a, Mel1b and GPR50. The transcription factors encoded by these genes, enzymes, transporters, prohormones, signaling and other proteins are involved in regulation of daily frequency.Despite the fact that the main components of the molecular genetic mechanisms of circadian rhythms are already known, the issue of regulating their work remains relevant today. The results of studies carried out on different populations with respect to individual polymorphic variants of genes are not always unambiguous and require a more detailed study, since it is the result of the interaction of genes that can determine their phenotypic effect.Thus, understanding the molecular mechanisms and identifying genetic markers that cause disturbances in circadian rhythms is an important step in the development of methods aimed at preventing and correcting pathological conditions caused by maladjustment processes.

адаптациястрессорные факторыциркадный ритм«часовые» геныadaptationstress factorscircadian rhythmclock genesАнализ литературных данных проведен в рамках проекта VI.62.1.8. «Разработка биопрепаратов из тканей растений и животных Якутии на основе изучения особенностей их биохимического состава и механизмов адаптации к условиям Севера» (№ 0376-2019-0005 регистрационный номер АААА-А17-117020110055-3) Института биологических проблем криолитозоны ФИЦ ЯНЦ СО РАН.Analysis of literature data was carried out within the framework of project VI.62.1.8. "Development of biological products from tissues of plants and animals of Yakutia on the basis of studying the peculiarities of their biochemical composition and mechanisms of adaptation to the conditions of the North" (No. 0376-2019-0005 registration number AAAA-A17-117020110055-3) of the Institute for Biological of Cryolithozone of the Siberian Brach of the RAS – Division of Federal Centre “The Yakut Scientific Centre of the Siberian Brach of the Russian Academy of Sciences”.ReferencesАнисимов В.Н. Эпифиз, биоритмы и старение организма / В.Н.Анисимов // Успехи физиол. наук. - 2010. - Т. 39 (4). - С. 40–65.Anisimov V.N. Epiphysis, biorhythms and aging of the body / V.N. Anisimov // Advances fiziol. sciences. – 2010. - T. 39 (4). - S. 40–65.Лопатина Н.Г. Гипотеза нервной регуляции процесса реализации наследственной информации / Н.Г. Лопатина, Г.П. Смирнова, В.В. Пономаренко // Проблемы высшей нервной деятельности и нейрофизиологии. Под ред. Н.Ф. Суворова. - Л., 1975. - С. 107–121.Lopatina N.G. Hypothesis of nervous regulation of the process of realization of hereditary information / N.G. Lopatina, G.P. Smirnova, V.V. Ponomarenko // Problems of higher nervous activity and neurophysiology. Ed. N.F. Suvorov. - L., 1975. - Р. 107-121.Ушаков И. Б. Адаптационный потенциал человека. / И. Б. Ушаков // Вестник РАМН. - 2004. - № 3. - С. 8-13.Ushakov I.B. Human adaptive potential / I.B. Ushakov // Bulletin of the Russian Academy of Medical Sciences. - 2004. - No. 3.- S. 8-13.Bedrosian T. Endocrine effects of circadian disruption / T. Bedrosian, L. Fonken, R. Annu Nelson // Rev. Physiol. - 2017. - Vol. 78.- P.109-131. DOI: 10.1146/annurev-physiol-021115-105102Bedrosian T. Endocrine effects of circadian disruption / T. Bedrosian, L. Fonken, R. Annu Nelson // Rev. Physiol. - 2017. - Vol. 78.- P.109-131. DOI: 10.1146/annurev-physiol-021115-105102Breakpoints of time in bed, midpoint of sleep, and social jetlag from infancy to early adulthood / C. Randler, C. Vollmer, N. Kalb et al. // Sleep Med. - 2019. - Vol. 57(80). - P. 86. DOI:10.1016/j.sleep.2019.01.023Breakpoints of time in bed, midpoint of sleep, and social jetlag from infancy to early adulthood / C. Randler, C. Vollmer, N. Kalb et al. // Sleep Med. - 2019. - Vol. 57(80). - P. 86. DOI:10.1016/j.sleep.2019.01.023Ekmekcioglu C. The melatonin receptor subtype MT2 is present in the human cardiovascular system / C. Ekmekcioglu, T. Thalhammer, S. Humpeler // J. Pineal. Res. - 2003. - Vol. 35 (1) :40-4.Ekmekcioglu C. The melatonin receptor subtype MT2 is present in the human cardiovascular system / C. Ekmekcioglu, T. Thalhammer, S. Humpeler // J. Pineal. Res. - 2003. - Vol. 35 (1) :40-4.Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms / E. Samuel, M. Jacqueline, Andrew R Wood et al. // Nature Communications. – 2019. - Vol. 10. – P. 343. DOI: 10.1038/s41467-018-08259-7.Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms / E. Samuel, M. Jacqueline, Andrew R Wood et al. // Nature Communications. – 2019. - Vol. 10. – P. 343. DOI: 10.1038/s41467-018-08259-7.Konopka R. Clock mutants in Drozophila melanogaster // R.Konopka, S. Benzer // Proc. Natl. Acad. Sci. U.S.A. - 1971. - Vol. 68. - P.2112-2116.Konopka R. Clock mutants in Drozophila melanogaster // R.Konopka, S. Benzer // Proc. Natl. Acad. Sci. U.S.A. - 1971. - Vol. 68. - P.2112-2116.Longitude position in a time zone and cancer risk in the United States / F.Gu, S. Xu, S. Devesa et al. // Cancer Epidemiol Prev Biomark. - 2017. - Vol. 26. - P.1306–1311. DOI: 10.1158/1055-9965.EPI-16-1029.Longitude position in a time zone and cancer risk in the United States / F.Gu, S. Xu, S. Devesa et al. // Cancer Epidemiol Prev Biomark. - 2017. - Vol. 26. - P.1306–1311. DOI: 10.1158/1055-9965.EPI-16-1029.Martha H. Genetics of Circadian Rhythms / H. Martha, S. Kazuhiro, J.Peng // Neurol Clin. - 2019. - Vol. 37(3). - P.487-504. DOI: 10.1016/j.ncl.2019.05.002.Martha H. Genetics of Circadian Rhythms / H. Martha, S. Kazuhiro, J.Peng // Neurol Clin. - 2019. - Vol. 37(3). - P.487-504. DOI: 10.1016/j.ncl.2019.05.002.Musiek E. Circadian clock disruption in neurodegenerative diseases: cause and effect? / E. Musiek // Front. Pharmacol. - 2015. - Vol. 6 (29). - P. 40–44.Musiek E. Circadian clock disruption in neurodegenerative diseases: cause and effect? / E. Musiek // Front. Pharmacol. - 2015. - Vol. 6 (29). - P. 40–44.Pittendrigh C. Temporal organization: reflections of a Darwinian clock-watcher / C. Pittendrigh // Ann. Rev. Physiol. - 1993. - Vol. 55(1). - P.17-54.Pittendrigh C. Temporal organization: reflections of a Darwinian clock-watcher / C. Pittendrigh // Ann. Rev. Physiol. - 1993. - Vol. 55(1). - P.17-54.Rijo-Ferreira F. Genomics of circadian rhythms in health and disease / F. Rijo-Ferreira, J. Takahashi // Genome Med.- 2019.- №11(1). - Vol.82. DOI: 10.1186/s13073-019-0704-0.Rijo-Ferreira F. Genomics of circadian rhythms in health and disease / F. Rijo-Ferreira, J. Takahashi // Genome Med.- 2019.- №11(1). - Vol.82. DOI: 10.1186/s13073-019-0704-0.Rönnlund M. Time perspective biases are associated with poor sleep quality, daytime sleepiness, and lower levels of subjective well-being among older adults / M. Rönnlund, M. Carelli // Front Psychol. - 2018. - Vol. 9. DOI:10.3389/fpsyg.2018.01356.Rönnlund M. Time perspective biases are associated with poor sleep quality, daytime sleepiness, and lower levels of subjective well-being among older adults / M. Rönnlund, M. Carelli // Front Psychol. - 2018. - Vol. 9. DOI:10.3389/fpsyg.2018.01356.Savvateeva-Popova E. Stress and genome lability: Drosophyla and Rat genetic models. In: Proceedings of the International Norway-Russian Startup PHAsE / E. Savvateeva-Popova, N. Dyuzhikova // Seminar “Physiological mechanisms of humans and animals in the processes of adaptation to environmental changes”. Saint Petersburg. - 2017. - P. 18-19.Savvateeva-Popova E. Stress and genome lability: Drosophyla and Rat genetic models. In: Proceedings of the International Norway-Russian Startup PHAsE / E. Savvateeva-Popova, N. Dyuzhikova // Seminar “Physiological mechanisms of humans and animals in the processes of adaptation to environmental changes”. Saint Petersburg. - 2017. - P. 18-19.Selye H. Conditioning by corticoids for the production of cardiac lesions with noradrenaline / H. Selye, E. Bajusz // Acta Endocrinol. - 1959. - Vol. 30. - P. 183–194.Selye H. Conditioning by corticoids for the production of cardiac lesions with noradrenaline / H. Selye, E. Bajusz // Acta Endocrinol. - 1959. - Vol. 30. - P. 183–194.Social jetlag and menstrual symptoms among female university students / Y. Komada, M. Ikeda Sato et al. // Chronobiol Int. - 2019. - Vol.36(2). - P.258–264. DOI:10.1080/07420528.2018.1533561.Social jetlag and menstrual symptoms among female university students / Y. Komada, M. Ikeda Sato et al. // Chronobiol Int. - 2019. - Vol.36(2). - P.258–264. DOI:10.1080/07420528.2018.1533561.The association between social jetlag, the metabolic syndrome, and type 2 diabetes mellitus in the general population: the new hoorn study / A. Koopman, S. Rauh, E. Van‘t Riet et al. // J. Biol. Rhythms. - 2017. - Vol. 32(4). - P.359–368. DOI: 10.1177/0748730417713572.The association between social jetlag, the metabolic syndrome, and type 2 diabetes mellitus in the general population: the new hoorn study / A. Koopman, S. Rauh, E. Van‘t Riet et al. // J. Biol. Rhythms. - 2017. - Vol. 32(4). - P.359–368. DOI: 10.1177/0748730417713572.The genetics of circadian rhythms, sleep and health / A. Jagannath, L. Taylor, Z. Wakaf et al. // Human Molecular Genetics. - 2017. - Vol. 26. - P.128 –138. DOI: 10.1093/hmg/ddx240The genetics of circadian rhythms, sleep and health / A. Jagannath, L. Taylor, Z. Wakaf et al. // Human Molecular Genetics. - 2017. - Vol. 26. - P.128 –138. DOI: 10.1093/hmg/ddx240

The authors declare that there are no conflicts of interest present.