problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl13278problendo-13278Research ArticleКлиническая эндокринологияClinical endocrinologyМолекулярные и клеточные механизмы старения: современные представления (обзор литературы)Molecular and cellular mechanisms of ageing: modern knowledge (literature review)https://orcid.org/0000-0001-5826-3186МихеевР. К.MikheevR. K.

Михеев Роберт Константинович

117036, г. Москва, ул. Дмитрия Ульянова, д. 11

SPIN-код: 9767-8468

Robert K. Mikheev, MD, resident

SPIN-код: 9767-8468

11 Dm. Ulyanova street, 117036 Moscow

iceberg1995@mail.ruhttps://orcid.org/0000-0001-8425-0020АндрееваЕ. Н.AndreevaE. N.

Андреева Елена Николаевна, д.м.н., профессор

SPIN-код: 1239-2937

Москва

Elena N. Andreeva, MD, PhD, professor

SPIN-код: 1239-2937

Moscow

endogin@mail.ruhttps://orcid.org/0000-0003-4979-7420ГригорянО. Р.GrigoryanO. R.

Григорян Ольга Рафаэльевна, д.м.н., профессор

SPIN-код: 3060-8242

Москва

Olga R. Grigoryan, MD, PhD, professor

SPIN-код: 3060-8242

Moscow

iceberg1995@mail.ruhttps://orcid.org/0000-0001-7177-0254ШереметьеваЕ. В.SheremetyevaE. V.

Шереметьева Екатерина Викторовна, к.м.н.

SPIN-код: 9413-5136

Москва

Ekaterina V. Sheremetyeva, MD, PhD

SPIN-код: 9413-5136

Moscow

s1981k@yandex.ruhttps://orcid.org/0000-0003-0696-5367АбсатароваЮ. С.AbsatarovaYu. S.

Абсатарова Юлия Сергеевна, к.м.н.

SPIN-код: 2220-9464

Москва

Yulia S. Absatarova, MD, PhD

Moscow

korsil2008@yandex.ruhttps://orcid.org/0000-0002-1044-142XОдарченкоА. С.OdarchenkoA. S.

Одарченко Арина Сергеевна

Москва

Arina S. Odarchenko, MD

Moscow

iceberg1995@mail.ruhttps://orcid.org/0000-0003-4356-3420ОплетаеваО. Н.OpletaevaO. N.

Оплетаева Олеся Николаевна, к.филос.н., доцент

SPIN-код: 3206-9425

Краснодар

Olesya N. Opletaeva, PhD, professor

SPIN-код: 3206-9425

Krasnodar

opleole@gmail.comНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian FederationНациональный медицинский исследовательский центр эндокринологии; Московский государственный медико-стоматологический университет им. А.И. ЕвдокимоваРоссияEndocrinology Research Centre; Moscow State University of Medicine and Dentistry of A.I. EvdokimovRussian FederationКубанский государственный технологический университетРоссияKuban State Technological UniversityRussian Federation2023111120236954554Copyright © Михеев Р.К., Андреева Е.Н., Григорян О.Р., Шереметьева Е.В., Абсатарова Ю.С., Одарченко А.С., Оплетаева О.Н., 20232023Михеев Р.К., Андреева Е.Н., Григорян О.Р., Шереметьева Е.В., Абсатарова Ю.С., Одарченко А.С., Оплетаева О.Н.Mikheev R.K., Andreeva E.N., Grigoryan O.R., Sheremetyeva E.V., Absatarova Y.S., Odarchenko A.S., Opletaeva 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://www.probl-endojournals.ru/jour/article/view/13278

Старение — запрограммированный на генетическом и эпигенетическом уровнях патофизиологический процесс, скорость которого определяется соотношением между факторами повреждения, с одной стороны, и факторами репарации организма — с другой. Старение является крайне актуальной проблемой не только в научном, но и в социально-демографическом плане. Согласно последним отчетам Всемирной организации здравоохранения (WHO, ВОЗ), общее число людей старше 60 лет продолжает неуклонно расти. Их общее число к 2020 г. уже достигло отметки в 1 млрд человек; при сохранении существующей тенденции к 2030 г. число пациентов достигнет отметки в 1,4 млрд, к 2050 г. — в 2,1 млрд человек. Отсутствие на сегодняшний день универсальной теории старения является поводом для научно-клинических изысканий с привлечением фундаментальных и клинических специалистов, в т.ч. эндокринологов. Ключевой интерес представляют последние данные о потенциальных источниках «anti-age лекарств»: натуральных и синтетических регуляторах теломераз, мезенхимальных стволовых клетках и т.д. Целью данного обзора литературы является освещение современных омиксных (геномных, протеомных, метаболомных) теорий старения, а также потенциальных способов таргетной (прицельной) профилактики и терапии возраст-ассоциированных заболеваний в рамках концепции персонализированной медицины. Данный обзор носит описательный характер, не преследует цель систематического обзора и метаанализа, а также рекламные цели. Представлена база данных PubMed за период с 1979 по 2022 гг.

Ageing (as known as eldering, senescence) is a genetically and epigenetically programmed pathophysiological process. Velocity of biological ageing is defined as balance between alteration and reparation of body structures. According to last World Health Organization (WHO) highlights ageing still stays an extremely actual scientific, social and demographic problem: in 2020 total number of people older than 60 years and older was 1 billion people; in 2030 future number may be 1,4 billion people, in 2050 — 2,1 billion people. Absence of single universal theory of aging nowadays is reason for scientifical and clinical collaboration between biologists and doctors, including endocrinologists. Designing of potentially effective newest anti-ageing strategies (such as natural/synthetic telomerase regulators, mesenchymal stem cells etc.) is of interest to scientific community. The aim of present article is a review of modern omics (genomic, proteomic, metabolomic) ageing mechanisms, potential ways of targeted prevention and treatment of age-related disease according to conception of personalized medicine. Present review is narrative, it does not lead to systematic review, meta-analysis and does not aim to commercial advertisement. Review has been provided via PubMed article that have been published since 1979 until 2022.

старениеомиксныйантивозрастнойтеломеразагеростимуляторыгеропротекторыagingomicsanti-ageingtelomerasegerostimulatorsgeroprotectorsИсследование проводится в рамках Государственного задания: «Влияние эпигенетических факторов на течение менопаузы у женщин с эндокринопатиями аутоиммунного генеза в рамках формирования модели “здорового старения”», регистрационный номер АААА-121030100033-4Lefever René The rehabilitation of irreversible processes and dissipative structures’ 50th anniversary Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 2018 06 20170365 376 2124 10.1098/rsta.2017.0365Tlidi M. Clerc M. G. Panajotov K. Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology, the legacy of Ilya Prigogine (part 1) Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 2018 06 20180114 376 2124 10.1098/rsta.2018.0114Tlidi M. Clerc M. G. Panajotov K. Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology, the legacy of Ilya Prigogine (part 2) Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 2018 11 20180276 376 2135 10.1098/rsta.2018.0276Bowen Richard L. Atwood Craig S. Living and Dying for Sex Gerontology 2004 08 265 290 50 5 10.1159/000079125World Health Organization. Owerview of Ageing [cited 24.09.23]. Available from: https://www.who.int/health-topics/ageing#tab=tab_1Haber C. Anti-Aging Medicine: The History: Life Extension and History: The Continual Search for the Fountain of Youth The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2011 06 B515 B522 59 6 10.1093/gerona/59.6.b515Cornaro L. The Art of Living Long (1558). Reprint. New York: Arno Press; 1979.Salameh Yasmeen Bejaoui Yosra El Hajj Nady DNA Methylation Biomarkers in Aging and Age-Related Diseases Frontiers in Genetics 2020 03 11 10.3389/fgene.2020.00171da Costa JP, Vitorino R, Silva GM, et al. A synopsis on aging—Theories, mechanisms and future prospects. Ageing Res Rev. 2016;(29):90-112. doi: https://doi.org/10.1016/j.arr.2016.06.005Johnson Thomas E. Increased Life-Span of age -1 Mutants in Caenorhabditis elegans and Lower Gompertz Rate of Aging Science 2006 10 908 912 249 4971 10.1126/science.2392681Tissenbaum Heidi A Ruvkun Gary An Insulin-like Signaling Pathway Affects Both Longevity and Reproduction in Caenorhabditis elegans Genetics 2021 07 703 717 148 2 10.1093/genetics/148.2.703Bin-Jumah May Nasser Nadeem Muhammad Shahid Gilani Sadaf Jamal Al-Abbasi Fahad A. Ullah Inam Alzarea Sami I. Ghoneim Mohammed M. Alshehri Sultan Uddin Aziz Murtaza Bibi Nazia Kazmi Imran Genes and Longevity of Lifespan International Journal of Molecular Sciences 2022 01 1499 23 3 10.3390/ijms23031499Peixoto Paul Cartron Pierre-François Serandour Aurélien A. Hervouet Eric From 1957 to Nowadays: A Brief History of Epigenetics International Journal of Molecular Sciences 2020 10 7571 21 20 10.3390/ijms21207571Bhakat Kishor K. Sengupta Shiladitya Mitra Sankar Fine-tuning of DNA base excision/strand break repair via acetylation DNA Repair 2020 10 102931 93 10.1016/j.dnarep.2020.102931Horvath Steve Raj Kenneth DNA methylation-based biomarkers and the epigenetic clock theory of ageing Nature Reviews Genetics 2018 04 371 384 19 6 10.1038/s41576-018-0004-3Princz A., Tavernarakis N. SUMOylation in Neurodegenerative Diseases // Gerontology. 2020. Vol. 66, № 2. P. 122–130.Koyuncu Seda Loureiro Rute Lee Hyun Ju Wagle Prerana Krueger Marcus Vilchez David Rewiring of the ubiquitinated proteome determines ageing in C. elegans Nature 2021 07 285 290 596 7871 10.1038/s41586-021-03781-zGroslambert Joséphine Prokhorova Evgeniia Ahel Ivan ADP-ribosylation of DNA and RNA DNA Repair 2021 06 103144 105 10.1016/j.dnarep.2021.103144Liu Gang Chen Haiying Liu Hua Zhang Wenbo Zhou Jia Emerging roles of SIRT6 in human diseases and its modulators Medicinal Research Reviews 2020 12 1089 1137 41 2 10.1002/med.21753Horvath Steve DNA methylation age of human tissues and cell types Genome Biology 2013 10 R115 14 10 10.1186/gb-2013-14-10-r115DNA Methylation Age Calculator. Available from: https://dnamage.genetics.ucla.edu/home//Bell CG, Lowe R, Adams PD, et al. DNA methylation aging clocks: challenges and recommendations. Genome Biol. 2019;20(1):249. doi: https://doi.org/10.1186/s13059-019-1824-yChan Michelle Yuan Han Soifer Ilya Maile Tobias M Wang Rebecca Y Ireland Andrea O'Brien Jonathon J Goudeau Jérôme Chan Leanne JG Vijay Twaritha Freund Adam Kenyon Cynthia Bennett Bryson D McAllister Fiona E Kelley David R Roy Margaret Cohen Robert L Levinson Arthur D Botstein David Hendrickson David G Novel insights from a multiomics dissection of the Hayflick limit eLife 2022 02 11 10.7554/elife.70283Perona Rosario The Nobel Prize in Physiology or Medicine 2009 “for telomere biology” and its relevance to cancer and related diseases Clinical and Translational Oncology 2010 10 647 649 12 10 10.1007/s12094-010-0572-yAguado Julio d’Adda di Fagagna Fabrizio Wolvetang Ernst Telomere transcription in ageing Ageing Research Reviews 2020 06 101115 62 10.1016/j.arr.2020.101115Lalonde Maxime Chartrand Pascal TERRA, a Multifaceted Regulator of Telomerase Activity at Telomeres Journal of Molecular Biology 2020 02 4232 4243 432 15 10.1016/j.jmb.2020.02.004Fragkiadaki Persefoni Renieri Elisavet Kalliantasi Katerina Kouvidi Elisavet Apalaki Evita Vakonaki Elena Mamoulakis Charalampos Spandidos Demetrios Tsatsakis Aristidis Τelomerase inhibitors and activators in aging and cancer: A systematic review Molecular Medicine Reports 2022 03 25 5 10.3892/mmr.2022.12674Wu L, Fidan K, Um J-Y, Ahn KS. Telomerase: Key regulator of inflammation and cancer. Pharmacol Res. 2020;(155):104726. doi: https://doi.org/10.1016/j.phrs.2020.104726Wang Yaqiang Sušac Lukas Feigon Juli Structural Biology of Telomerase Cold Spring Harbor Perspectives in Biology 2019 08 a032383 11 12 10.1101/cshperspect.a032383Bousso Philippe Wahn Volker Douagi Iyadh Horneff Gerd Pannetier Christophe Le Deist Françoise Zepp Fred Niehues Tim Kourilsky Philippe Fischer Alain de Saint Basile Geneviève Diversity, functionality, and stability of the T cell repertoire derived in vivo from a single human T cell precursor Proceedings of the National Academy of Sciences 2002 07 274 278 97 1 10.1073/pnas.97.1.274Pereira Branca Xu Xiao-Ning Akbar Arne N. Targeting Inflammation and Immunosenescence to Improve Vaccine Responses in the Elderly Frontiers in Immunology 2020 10 11 10.3389/fimmu.2020.583019Das Melanie M. Godoy Marlesa Chen Shuang Moser V. Alexandra Avalos Pablo Roxas Kristina M. Dang Ivy Yáñez Alberto Zhang Wenxuan Bresee Catherine Arditi Moshe Liu George Y. Svendsen Clive N. Goodridge Helen S. Young bone marrow transplantation preserves learning and memory in old mice Communications Biology 2019 02 2 1 10.1038/s42003-019-0298-5Uziel Orit Lahav Meir Shargian Liat Beery Einat Pasvolsky Oren Rozovski Uri Raanani Pia Yeshurun Moshe Premature ageing following allogeneic hematopoietic stem cell transplantation Bone Marrow Transplantation 2020 02 1438 1446 55 7 10.1038/s41409-020-0839-zEpelbaum J. Neuroendocrinology and Aging Journal of Neuroendocrinology 2008 06 808 811 20 6 10.1111/j.1365-2826.2008.01720.xIwen K. A. Brabant G. Therapie mit Schilddrüsenhormonen im Alter Der Internist 2020 04 541 548 61 6 10.1007/s00108-020-00790-4Corona Giovanni Krausz Csilla Late‐onset hypogonadism a challenging task for the andrology field Andrology 2020 11 1504 1505 8 6 10.1111/andr.12917Tan Dun Xu Bing Zhou Xinjia Reiter Russel Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland Molecules 2018 01 301 23 2 10.3390/molecules23020301Gambacciani Marco Levancini Marco Featured Editorial Hormone replacement therapy and the prevention of postmenopausal osteoporosis Menopausal Review 2014 09 213 220 4 10.5114/pm.2014.44996HILL M. TŘÍSKALA Z. HONCŮ P. KREJČÍ M. KAJZAR J. BIČÍKOVÁ M. ONDŘEJÍKOVÁ L. JANDOVÁ D. STERZL I. Aging, Hormones and Receptors Physiological Research 2020 10 S255 S272 10.33549/physiolres.934523Schumacher Björn Pothof Joris Vijg Jan Hoeijmakers Jan H. J. The central role of DNA damage in the ageing process Nature 2021 04 695 703 592 7856 10.1038/s41586-021-03307-7Carusillo Antonio Mussolino Claudio DNA Damage: From Threat to Treatment Cells 2020 07 1665 9 7 10.3390/cells9071665Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ Mol Mutagen. 2017;58(5):235-263. doi: https://doi.org/10.1002/em.22087Shi Tao Dansen Tobias B. Reactive Oxygen Species Induced p53 Activation: DNA Damage, Redox Signaling, or Both? Antioxidants & Redox Signaling 2020 03 839 859 33 12 10.1089/ars.2020.8074Chen Xing Fu Wenyan Luo Yangchao Cui Chun Suppavorasatit Inthawoot Liang Li Protein deamidation to produce processable ingredients and engineered colloids for emerging food applications Comprehensive Reviews in Food Science and Food Safety 2021 05 3788 3817 20 4 10.1111/1541-4337.12759Galzio R. Rosati F. Benedetti E. Cristiano L. Aldi S. Mei S. D'Angelo B. Gentile R. Laurenti G. Cifone M.G. Giordano A. Cimini A. Glycosilated nucleolin as marker for human gliomas Journal of Cellular Biochemistry 2011 09 571 579 113 2 10.1002/jcb.23381Fielden John Ruggiano Annamaria Popović Marta Ramadan Kristijan DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans DNA Repair 2018 08 198 204 71 10.1016/j.dnarep.2018.08.025López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013;153(6):1194-1217. doi: https://doi.org/10.1016/j.cell.2013.05.039Geng Yinan Yang Jinxiu Li Shiyi Chen Minliang Chyloid Fat Carried Adipose-Derived Mesenchymal Stem Cells Accelerate Wound Healing Via Promoting Angiogenesis Annals of Plastic Surgery 2021 06 472 477 87 4 10.1097/sap.0000000000002778Shyh-Chang Ng Ng Huck-Hui The metabolic programming of stem cells Genes & Development 2017 03 336 346 31 4 10.1101/gad.293167.116Simonson Oscar E. Mougiakakos Dimitrios Heldring Nina Bassi Giulio Johansson Henrik J. Dalén Magnus Jitschin Regina Rodin Sergey Corbascio Matthias El Andaloussi Samir Wiklander Oscar P.B. Nordin Joel Z. Skog Johan Romain Charlotte Koestler Tina Hellgren-Johansson Laila Schiller Petter Joachimsson Per-Olof Hägglund Hans Mattsson Mattias Lehtiö Janne Faridani Omid R. Sandberg Rickard Korsgren Olle Krampera Mauro Weiss Daniel J. Grinnemo Karl-Henrik Le Blanc Katarina In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome Stem Cells Translational Medicine 2015 08 1199 1213 4 10 10.5966/sctm.2015-0021Simonson Oscar E. Ståhle Elisabeth Hansen Tomas Wedin Johan O. Larsson Anders Mattsson Mattias Volchkov Pavel Le Blanc Katarina Rodin Sergey Grinnemo Karl-Henrik Five-Year Follow-up after Mesenchymal Stromal Cell–based Treatment of Severe Acute Respiratory Distress Syndrome American Journal of Respiratory and Critical Care Medicine 2020 06 1051 1055 202 7 10.1164/rccm.202003-0544leKelly Kilian Rasko John E. J. Mesenchymal Stromal Cells for the Treatment of Graft Versus Host Disease Frontiers in Immunology 2021 10 12 10.3389/fimmu.2021.761616Shabbir Umair Arshad Muhammad Sajid Sameen Aysha Oh Deog-Hwan Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies Nutrients 2021 02 690 13 2 10.3390/nu13020690Liu S, Gao J, Zhu M, Liu K, Zhang H-L. Gut microbiota and dysbiosis in Alzheimer’s disease: Implications for pathogenesis and treatment. Mol Neurobiol. 2020;57(12):5026-5043. doi: https://doi.org/10.1007/s12035-020-02073-3Sun Jing Xu Jingxuan Ling Yi Wang Fangyan Gong Tianyu Yang Changwei Ye Shiqing Ye Keyue Wei Dianhui Song Ziqing Chen Danna Liu Jiaming Fecal microbiota transplantation alleviated Alzheimer’s disease-like pathogenesis in APP/PS1 transgenic mice Translational Psychiatry 2019 08 9 1 10.1038/s41398-019-0525-3Buchanan Sarah Combet Emilie Stenvinkel Peter Shiels Paul G. Klotho, Aging, and the Failing Kidney Frontiers in Endocrinology 2020 08 11 10.3389/fendo.2020.00560

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