Роль сна в процессах старения

Сон, являясь жизненно необходимой потребностью организма, связан со многими важными биологическими процессами. Старение — один из естественных биологических процессов, оказывающих влияние на все функции человеческого организма. Изучение связи между сном и старением вызывает оживленный интерес исследователей в последние годы. В статье обсуждаются современные взгляды о роли сна в процессах старения и его геропротективный потенциал. В статье приводятся данные по изучению влияния нарушения сна на ключевые признаки старения. Обсуждается влияние депривации сна, инсомнии и синдрома обструктивного апноэ сна на девять ключевых признаков старения, выделенных López-Otín C. и соавторами: нестабильность генома, укорочение теломер, потерю протеостаза, эпигенетические модификации, нарушение распознавания питательных веществ, дисфункцию митохондрий, истощение пула стволовых клеток, клеточное старение и изменение внутриклеточного взаимодействия. Также приводятся данные о сомнологических биомаркерах и их связи с индексом возраста мозга, затрагиваются вопросы влияния сна на формирование нейродегенеративных расстройств, в том числе болезни Альцгеймера. Один из разделов посвящен обзору данных литературы на тему значимости циркадных ритмов в развитии нейродегенерации и процессов старения. В качестве геропротективных методов рассматривается применение светотерапии и мелатонина. В заключении обсуждается актуальность развития геронтосомнологии.

1. Miletínová E., Bušková J. Functions of Sleep. Physiol Res. 2021;70(2):177-182. doi: 10.33549/physiolres.934470

2. Freund W., Weber F. The Function of Sleep and the Treatment of Primary Insomnia. Dtsch Arztebl Int. 2023;120(50):863-870. doi: 10.3238/arztebl.m2023.0228

3. Cirelli C. Brain plasticity, sleep and aging. Gerontology. 2012;58(5):441-445. doi: 10.1159/000336149

4. Liu H., Byles J.E., Xu X., et al. Association between nighttime sleep and successful aging among older Chinese people. Sleep Med. 2016;22:18-24. doi: 10.1016/j.sleep.2016.04.016

5. Xin C., Zhang B., Fang S., et al. Daytime napping and successful aging among older adults in China: a cross-sectional study. BMC Geriatr. 2020;20(1):2. doi: 10.1186/s12877-019-1408-4

6. Miner B., Kryger M.H. Sleep in the Aging Population. Sleep Med Clin. 2020;15(2):311-318. doi: 10.1016/j.jsmc.2020.02.016

7. Jagota A. Sleep and circadian clock: novel players in health impacts and aging. In: Sleep and clocks in aging and longevity. Springer International Publishing. 2023;3–31.

8. Tang J.Y., Luo H., Tse M., et al. The relationship between insomnia symptoms and frailty in community-dwelling older persons: a path analysis. Sleep Med. 2021;84:237-243. doi: 10.1016/j.sleep.2021.05.039

9. Soyeux L. Geriatric Sleep Medicine, a Young Field. Chronobiology in Medicine. 2019;1:93-94. doi: 10.33069/cim.2019.0014

10. Исаев Р.И., Мхитарян Э.А., Василевская В.В. и др. Нарушения сна в гериатрии. Проблемы геронауки. 2024; 2(6): 75– 85. doi: 10.37586/2949-4745-2-2024-75-85

11. Carvalhas-Almeida C., Cavadas C., Álvaro A.R. The impact of insomnia on frailty and the hallmarks of aging. Aging Clin Exp Res. 2023;35(2):253-269. doi: 10.1007/s40520-022-02310-w

12. López-Otín C., Blasco M.A., Partridge L., et al. The hallmarks of aging. Cell. 2013;153(6):1194-1217. doi: 10.1016/j.cell.2013.05.039

13. Gaspar L.S., Álvaro A.R., Moita J., et al. Obstructive Sleep Apnea and Hallmarks of Aging. Trends Mol Med. 2017;23(8):675-692. doi: 10.1016/j.molmed.2017.06.006

14. Carskadon M.A., Chappell K.R., Barker D.H., et al. A pilot prospective study of sleep patterns and DNA methylation-characterized epigenetic aging in young adults. BMC Res Notes. 2019;12(1):583. doi: 10.1186/s13104-019-4633-1

15. Pace-Schott E.F., Spencer R.M. Sleep-dependent memory consolidation in healthy aging and mild cognitive impairment. Curr Top Behav Neurosci. 2015;25:307-330. doi: 10.1007/7854_2014_300

16. Casagrande M., Forte G., Favieri F., et al. Sleep Quality and Aging: A Systematic Review on Healthy Older People, Mild Cognitive Impairment and Alzheimer's Disease. Int J Environ Res Public Health. 2022;19(14):8457. doi: 10.3390/ijerph19148457

17. Bah T.M., Goodman J., Iliff J.J. Sleep as a Therapeutic Target in the Aging Brain. Neurotherapeutics. 2019;16(3):554-568. doi: 10.1007/s13311-019-00769-6

18. Mander B.A., Winer J.R., Jagust W.J., et al. Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease? Trends Neurosci. 2016;39(8):552-566. doi: 10.1016/j.tins.2016.05.002

19. Kryger M., Roth T., Dement W. Principles and Practice of Sleep Medicine. 6th Edition. 2017.

20. Senaratna C.V., Perret J.L., Lodge C.J., et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev. 2017;34:70-81. doi: 10.1016/j.smrv.2016.07.002

21. Полуэктов М.Г., Стрыгин К.Н. Расстройства сна в пожилом возрасте. Медицинский совет. 2014;5:74-81.

22. Schmauck-Medina T., Molière A., Lautrup S., et al. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging (Albany NY). 2022;14(16):6829-6839. doi: 10.18632/aging.204248

23. Yamauchi M., Nakano H., Maekawa J., et al. Oxidative stress in obstructive sleep apnea. Chest. 2005;127(5):1674-1679. doi: 10.1378/ chest.127.5.1674

24. Kontogianni K., Messini-Nikolaki N., Christou K., et al. DNA damage and repair capacity in lymphocytes from obstructive sleep apnea patients. Environ Mol Mutagen. 2007;48(9):722-727. doi: 10.1002/em.20351

25. Xie J., Jiang J., Shi K., et al. DNA damage in peripheral blood lymphocytes from patients with OSAHS. Sleep Breath. 2014;18(4):775- 780. doi: 10.1007/s11325-014-0942-8

26. Carroll J.E., Esquivel S., Goldberg A., et al. Insomnia and Telomere Length in Older Adults. Sleep. 2016;39(3):559-564. doi: 10.5665/sleep.5526

27. Fenech M., Kirsch-Volders M., Natarajan A.T., et al. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis. 2011;26(1):125- 132. doi: 10.1093/mutage/geq052

28. Carroll J.E., Cole S.W., Seeman T.E., et al. Partial sleep deprivation activates the DNA damage response (DDR) and the senescenceassociated secretory phenotype (SASP) in aged adult humans. Brain Behav Immun. 2016;51:223-229. doi: 10.1016/j.bbi.2015.08.024

29. Zhang X., Wang Y., Zhao R., et al. Folic Acid Supplementation Suppresses Sleep Deprivation-Induced Telomere Dysfunction and Senescence-Associated Secretory Phenotype (SASP). Oxid Med Cell Longev. 2019;2019:4569614. doi: 10.1155/2019/4569614

30. Garland S.N., Palmer C., Donelson M., et al. A nested casecontrolled comparison of telomere length and psychological functioning in breast cancer survivors with and without insomnia symptoms. Rejuvenation Res. 2014;17(5):453-457. doi: 10.1089/rej.2014.1586

31. Tempaku P.F., Mazzotti D.R., Hirotsu C., et al. The effect of the severity of obstructive sleep apnea syndrome on telomere length. Oncotarget. 2016;7(43):69216-69224. doi: 10.18632/oncotarget.12293

32. Riestra P., Gebreab S.Y., Xu R., et al. Obstructive sleep apnea risk and leukocyte telomere length in African Americans from the MH-GRID study. Sleep Breath. 2017;21(3):751-757. doi: 10.1007/ s11325-016-1451-8

33. Стражеско И.Д., Есакова А.П., Акопян А.А. и др. Эпигенетика старения: основные механизмы. Проблемы геронауки. 2023;2:88–93. doi: 10.37586/2949-4745-2-2023-88-93

34. Carroll J.E., Irwin M.R., Levine M., et al. Epigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings From the Women's Health Initiative Study. Biol Psychiatry. 2017;81(2):136-144. doi: 10.1016/j.biopsych.2016.07.008

35. Trivedi M.S., Holger D., Bui A.T., et al. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status. PLoS One. 2017;12(7):e0181978. doi: 10.1371/journal. pone.0181978

36. Chen Y.C., Chen T.W., Su M.C., et al. Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype. Sleep. 2016;39(4):743-755. doi: 10.5665/sleep.5620

37. Cortese R., Zhang C., Bao R., et al. DNA Methylation Profiling of Blood Monocytes in Patients With Obesity Hypoventilation Syndrome: Effect of Positive Airway Pressure Treatment. Chest. 2016;150(1):91-101. doi: 10.1016/j.chest.2016.02.648

38. Campisi J., d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8(9):729-740. doi: 10.1038/nrm2233

39. Бородкина А.В., Дерябин П.И., Грюкова А.А. и др. «Социальная жизнь» стареющих клеток: что такое SASP и зачем его изучать? Acta Naturae (русскоязычная версия). 2018;10(1(36)):4-15.

40. Sancar A., Lindsey-Boltz L.A., Kang T.H., et al. Circadian clock control of the cellular response to DNA damage. FEBS Lett. 2010;584(12):2618-2625. doi: 10.1016/j.febslet.2010.03.017

41. Sun N., Youle R.J., Finkel T. The Mitochondrial Basis of Aging. Mol Cell. 2016;61(5):654-666. doi: 10.1016/j.molcel.2016.01.028

42. Schulz R., Mahmoudi S., Hattar K., et al. Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med. 2000;162 (2Pt 1):566-570. doi: 10.1164/ajrccm.162.2.9908091

43. Dyugovskaya L., Lavie P., Lavie L. Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med. 2002;165(7):934- 939. doi: 10.1164/ajrccm.165.7.2104126

44. Carpagnano G.E., Kharitonov S.A., Resta O., et al. 8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy. Chest. 2003;124(4):1386-1392. doi: 10.1378/chest.124.4.1386

45. Barceló A., Barbé F., de la Peña M., et al. Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment. Eur Respir J. 2006;27(4):756-760. doi: 10.1183/09031936.06.00067605

46. Saner N.J., Lee M.J., Kuang J., et al. Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms. Mol Metab. 2021;43:101110. doi: 10.1016/j.molmet.2020.101110

47. Zhao H., Wu H., He J., et al. Frontal cortical mitochondrial dysfunction and mitochondria-related β-amyloid accumulation by chronic sleep restriction in mice. Neuroreport. 2016;27(12):916-922. doi: 10.1097/WNR.0000000000000631

48. Ильинский Н.С., Нестеров С.В., Шестоперова Е.И. и др. Роль естественных процессов старения в возникновении и патогенезе болезней, связанных с аномальным накоплением белковых агрегатов. Биохимия. 2021;86(3):324-340.

49. Kaushik S., Cuervo A.M. Proteostasis and aging. Nat Med. 2015;21(12):1406-1415. doi: 10.1038/nm.4001

50. Cedernaes J., Schönke M., Westholm J.O., et al. Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans. Sci Adv. 2018;4(8):eaar8590. doi: 10.1126/sciadv.aar8590

51. Noguchi T., Chin K., Ohi M., et al. Heat shock protein 72 level decreases during sleep in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 1997;155(4):1316-1322. doi: 10.1164/ajrccm.155.4.9105073

52. Barzilai N., Huffman D.M., Muzumdar R.H., et al. The critical role of metabolic pathways in aging. Diabetes. 2012;61(6):1315-1322. doi: 10.2337/db11-1300

53. Gileles-Hillel A., Kheirandish-Gozal L., Gozal D. Biological plausibility linking sleep apnoea and metabolic dysfunction. Nat Rev Endocrinol. 2016;12(5):290-298. doi: 10.1038/nrendo.2016.22

54. Kim C.E., Shin S., Lee H.W., et al. Association between sleep duration and metabolic syndrome: a cross-sectional study. BMC Public Health. 2018;18(1):720. doi: 10.1186/s12889-018-5557-8

55. Syauqy A., Hsu C.Y., Rau H.H., et al. Association of Sleep Duration and Insomnia Symptoms with Components of Metabolic Syndrome and Inflammation in Middle-Aged and Older Adults with Metabolic Syndrome in Taiwan. Nutrients. 2019;11(8):1848. doi: 10.3390/nu11081848

56. Zhang Y., Jiang X., Liu J., et al. The association between insomnia and the risk of metabolic syndrome: A systematic review and meta-analysis [published correction appears in J Clin Neurosci. 2021 Nov;93:287]. J Clin Neurosci. 2021;89:430-436. doi: 10.1016/j.jocn.2021.05.039

57. Ip M.S., Lam B., Ng M.M., et al. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med. 2002;165(5):670-676. doi: 10.1164/ajrccm.165.5.2103001

58. Punjabi N.M., Shahar E., Redline S., et al. Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol. 2004;160(6):521-530. doi: 10.1093/aje/ kwh261

59. Punjabi N.M., Beamer B.A. Alterations in Glucose Disposal in Sleep-disordered Breathing. Am J Respir Crit Care Med. 2009;179(3):235-240. doi: 10.1164/rccm.200809-1392OC

60. Polotsky V.Y., Patil S.P., Savransky V., et al. Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity [published correction appears in Am J Respir Crit Care Med. 2009 Nov 1;180(9):910-1]. Am J Respir Crit Care Med. 2009;179(3):228-234. doi: 10.1164/rccm.200804-608OC

61. Harsch I.A., Schahin S.P., Radespiel-Tröger M., et al. Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2004;169(2):156-162. doi: 10.1164/rccm.200302-206OC

62. Lam J.C., Lam B., Yao T.J., et al. A randomised controlled trial of nasal continuous positive airway pressure on insulin sensitivity in obstructive sleep apnoea. Eur Respir J. 2010;35(1):138-145. doi: 10.1183/09031936.00047709

63. Naidoo N., Davis J.G., Zhu J., et al. Aging and sleep deprivation induce the unfolded protein response in the pancreas: implications for metabolism. Aging Cell. 2014;13(1):131-141. doi: 10.1111/acel.12158

64. Kheirandish-Gozal L., Bhattacharjee R., Kim J., et al. Endothelial progenitor cells and vascular dysfunction in children with obstructive sleep apnea. Am J Respir Crit Care Med. 2010;182(1):92-97. doi: 10.1164/rccm.200912-1845OC

65. Almendros I., Carreras A., Montserrat J.M., et al. Potential role of adult stem cells in obstructive sleep apnea. Front Neurol. 2012;3:112. doi: 10.3389/fneur.2012.00112

66. Jelic S., Lederer D.J., Adams T., et al. Endothelial repair capacity and apoptosis are inversely related in obstructive sleep apnea. Vasc Health Risk Manag. 2009;5:909-920. doi: 10.2147/vhrm.s8123

67. Hinojosa-Godinez A., Jave-Suarez L.F., Flores-Soto M., et al. Melatonin modifies SOX2+ cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation. Neural Regen Res. 2019;14(10):1787-1795. doi: 10.4103/1673-5374.257537

68. Gianotti L., Pivetti S., Lanfranco F., et al. Concomitant impairment of growth hormone secretion and peripheral sensitivity in obese patients with obstructive sleep apnea syndrome. J Clin Endocrinol Metab. 2002;87(11):5052-5057. doi: 10.1210/jc.2001-011441

69. Ursavas A., Karadag M., Ilcol Y.O., et al. Low level of IGF-1 in obesity may be related to obstructive sleep apnea syndrome. Lung. 2007;185(5):309-314. doi: 10.1007/s00408-007-9026-x

70. Spiegel K., Follenius M., Krieger J., et al. Prolactin secretion during sleep in obstructive sleep apnoea patients. J Sleep Res. 1995;4(1):56-62. doi: 10.1111/j.1365-2869.1995.tb00151.x

71. Vasisht K.P., Kessler L.E., Booth J.N. 3rd, et al. Differences in insulin secretion and sensitivity in short-sleep insomnia. Sleep. 2013;36(6):955-957. doi: 10.5665/sleep.2734

72. Чердак М.А. Старение головного мозга. Проблемы геронауки. 2023;2:71–79. doi: 10.37586/2949-4745-2-2023-71-79

73. Bishir M., Bhat A., Essa M.M., et al. Sleep Deprivation and Neurological Disorders. Biomed Res Int. 2020 Nov 23;2020:5764017. doi: 10.1155/2020/5764017.

74. Боголепова А.Н., Васенина Е.Е., Гомзякова Н.А. и др. Клинические рекомендации «Когнитивные расстройства у пациентов пожилого и старческого возраста». Журнал неврологии и психиатрии им. С.С. Корсакова. 2021;121(10-3):6–137. doi: 10.17116/ jnevro20211211036

75. Исаев Р.И., Яхно Н.Н. Нарушения сна при болезни Альцгеймера. Неврологический журнал. 2017;(5).

76. Bubu O.M., Brannick M., Mortimer J., et al. Sleep, cognitive impairment and Alzheimer’s disease: A systematic review and metaanalysis. Sleep. 2016; pii: sp-00173-16.

77. Sterniczuk R, Theou O, Rusak B, et al. Sleep disturbance is associated with incident dementia and mortality. Curr Alzheimer Res. 2013;10(7):767-75. doi: 10.2174/15672050113109990134

78. Яковлева О.В., Полуэктов М.Г., Левин О.С., и др. Нарушения сна и бодрствования при нейродегенеративных заболеваниях. Журнал неврологии и психиатрии им. С.С. Корсакова. Спецвыпуски. 2018;118(42):8391. doi: 10.17116/jnevro20181184283

79. Spira A.P., Gamaldo A.A., An Y.,et al. Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurol. 2013;70(12):1537-43. doi: 10.1001/jamaneurol.2013.4258

80. Azam S., Haque M.E., Balakrishnan R., et al. The Ageing Brain: Molecular and Cellular Basis of Neurodegeneration. Front Cell Dev Biol. 2021;13;9:683459. doi: 10.3389/fcell.2021.683459

81. Isaev N.K., Stelmashook E.V., Genrikhs E.E. Neurogenesis and brain aging. Rev Neurosci. 2019;26;30(6):573-580. doi: 10.1515/revneuro-2018-0084

82. Lundgaard I., Lu M.L., Yang E., et al. Glymphatic clearance controls state-dependent changes in brain lactate concentration. J Cereb Blood Flow Metab. 2017;37:2112–2124.

83. Iliff J.J., Lee H., Yu M., et al. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest. 2013;123:1299–1309.

84. Holth J.K., Fritschi S.K., Wang C., et al. The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science. 2019;363(6429):880-884. doi: 10.1126/science.aav2546

85. Gordleeva S., Kanakov O., Ivanchenko M., et al. Brain aging and garbage cleaning : Modelling the role of sleep, glymphatic system, and microglia senescence in the propagation of inflammaging. Semin Immunopathol. 2020;42(5):647-665. doi: 10.1007/s00281-020-00816-x

86. Nedergaard M., Goldman S.A. Brain drain. Sci Am. 2016;314(3):44-9. doi: 10.1038/scientificamerican0316-44

87. Xie L., et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342:373–377.

88. Villafuerte G., et al. Sleep deprivation and oxidative stress in animal models: a systematic review. Oxid Med Cell Longev. 2015;2015:234952.

89. Dworak M., et al. Sleep and brain energy levels: ATP changes during sleep. J Neurosci. 2010;30:9007–9016.

90. Everson C.A., et al. Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats. Sleep. 2014;37:1929–1940.

91. Mander B.A., et al. beta-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat Neurosci. 2015;18:1051–1057.

92. Roh J.H., et al. Disruption of the sleep-wake cycle and diurnal fluctuation of beta-amyloid in mice with Alzheimer's disease pathology. Sci Transl Med. 2012;4:150ra122.

93. Kress B.T., Iliff J.J., Xia M., et al. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol. 2014;76(6):845-61. doi: 10.1002/ana.24271

94. Zhou Y., Cai J., Zhang W., et al. Impairment of the Glymphatic Pathway and Putative Meningeal Lymphatic Vessels in the Aging Human. Ann Neurol. 2020;87(3):357-369. doi: 10.1002/ana.25670

95. Zavecz Z., Shah V.D., Murillo O.G., et al. NREM sleep as a novel protective cognitive reserve factor in the face of Alzheimer's disease pathology. BMC Med. 2023;21(1):156. doi: 10.1186/s12916-023-02811-z

96. Da Mesquita S., Papadopoulos Z., Dykstra T., et al. Meningeal Lymphatics Affect Microglia Responses and Anti-Aβ Immunotherapy. Nature. 2021;593:255–260. doi: 10.1038/s41586-021-03489-0

97. Blinkouskaya Y., Caçoilo A., Gollamudi T., et al. Brain aging mechanisms with mechanical manifestations. Mech Ageing Dev. 2021;200:111575. doi: 10.1016/j.mad.2021.111575

98. Sun H., Paixao L., Oliva J.T., et al. Brain age from the electroencephalogram of sleep. Neurobiol Aging. 2019;74:112-120. doi: 10.1016/j.neurobiolaging.2018.10.016

99. Mander B.A., Winer J.R., Walker M.P. Sleep and Human Aging. Neuron. 2017;94(1):19-36. doi: 10.1016/j.neuron.2017.02.004

100. Scullin M.K. Do Older Adults Need Sleep? A Review of Neuroimaging, Sleep, and Aging Studies. Curr Sleep Med Rep. 2017;3(3):204-214. doi: 10.1007/s40675-017-0086-z

101. Carrier J., Land S., Buysse D.J., et al. The effects of age and gender on sleep EEG power spectral density in the middle years of life (ages 20-60 years old). Psychophysiology. 2001;38(2):232-42.

102. Larsen L.H., Moe K.E., Vitiello M.V., et al. Age trends in the sleep EEG of healthy older men and women. J. Sleep Res. 1995;4, 160e172.

103. Purcell S.M., Manoach D.S., Demanuele C., et al. Characterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource. Nat Commun. 2017;8:15930. doi: 10.1038/ncomms15930

104. Paixao L., Sikka P., Sun H., et al. Excess brain age in the sleep electroencephalogram predicts reduced life expectancy. Neurobiol Aging. 2020;88:150-155. doi: 10.1016/j.neurobiolaging.2019.12.015

105. Yook S., Park H.R., Park C., et al. Novel neuroelectrophysiological age index associated with imaging features of brain aging and sleep disorders. Neuroimage. 2022;264:119753. doi: 10.1016/j.neuroimage.2022.119753

106. Czeisler С.А. Buxton О.М. Human Circadian Timing System and Sleep-Wake Regulation // Principles and Practice of Sleep Medicine. 6th Edition. 2017.

107. Gurcharan Kaur et al. Brain and Mental Health in Ageing. 2024.

108. Thompson K.I., Chau M., Lorenzetti M.S., et al. Acute sleep deprivation disrupts emotion, cognition, inflammation, and cortisol in young healthy adults. Front Behav Neurosci. 2022;16:945661.

109. Yeager M.P., Pioli P.A., Guyre P.M. Cortisol exerts bi-phasic regulation of inflammation in humans. Dose-Response. 2011;9(3).

110. Jones C., Gwenin C. Cortisol level dysregulation and its prevalence—is it nature’s alarm clock? Physiol Rep. 2021;8(24):14644.

111. Abbott S.A., Malkani R.G., Zee P.Z. Circadian Dysregulation in Mental and Physical Health // Principles and Practice of Sleep Medicine. 6th Edition. 2017.

112. Kim S.J., Lim Y.C., Suh I.B., et al. Disrupted sleep maintenance is associated with altered circadian phase and phase angle in community-dwelling adults. Sleep Med. 2020;73:250-256.

113. Humpston C., Benedetti F., Serfaty M., et al. Chronotherapy for the rapid treatment of depression: a meta-analysis. J Affect Disord. 2020;261:91-102.