vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-26vavilov-4092Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSРоль сиртуинов в эпигенетической регуляции и контроле старенияRole of sirtuins in epigenetic regulation and aging controlСамойловаЕ. М.SamoilovaE. M.

Новосибирск

Москва

Novosibirsk

Moscow

РомановС. Е.RomanovS. E.

Новосибирск

Novosibirsk

ЧудаковаД. А.ChudakovaD.  A.

Москва

Moscow

ЛактионовП. П.LaktionovP. P.

Новосибирск

Novosibirsk

laktionov@mcb.nsc.ruНовосибирский национальный исследовательский государственный университет; Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наукРоссияNovosibirsk State University; Engelhardt Institute of Molecular Biology of the Russian Academy of SciencesRussian FederationНовосибирский национальный исследовательский государственный университет; Институт молекулярной и клеточной биологии Сибирского отделения Российской академии наукРоссияNovosibirsk State University; Institute of Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный центр мозга и нейротехнологий Федерального медико­биологического агентства РоссииРоссияFederal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency of RussiaRussian Federation202411042024282215­-227Copyright © Самойлова Е.М., Романов С.Е., Чудакова Д.А., Лактионов П.П., 20242024Самойлова Е.М., Романов С.Е., Чудакова Д.А., Лактионов П.П.Samoilova E.M., Romanov S.E., Chudakova D.A., Laktionov P.P.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4092

Достижения современного здравоохранения в развитых странах позволили увеличить продолжительность жизни, из­-за чего все более актуальным становится сохранение активного долголетия. С момента открытия белки семейства сиртуинов рассматривались в качестве значимых регуляторов физиологических процессов, ассоциированных со старением. Сиртуины проявляют деацетилазную, деацилазную, АДФ­рибозилтрансферазную активность и модифицируют множество белковых субстратов, включая компоненты хроматина и регуляторные белки. Столь многофакторная система регуляции затрагивает ряд процессов, таких как клеточный метаболизм, функции митохондрий, эпигенетическую регуляцию, репарацию ДНК и прочие. Неудивительно, что активность белков­сиртуинов затрагивает проявление классических признаков старения организма: клеточное старение, нарушения метаболизма, митохондриальную дисфункцию, геномную нестабильность и нарушение эпигенетической регуляции. Непосредственное изменение активности сиртуинов в клетках человека также рассматривается в качестве маркера старения и вовлечено в генез различных возраст-­зависимых патологических состояний. Кроме того, экспериментальные данные, полученные на модельных животных, а также результаты популяционных геномных исследований позволяют предположить влияние сиртуинов на продолжительность жизни. Вместе с тем многообразие функций сиртуинов и биохимических субстратов делает крайне нетривиальным выявление причинно-­следственных связей и непосредственной роли сиртуинов в контроле функционального состояния организма. Однако влияние сиртуинов на эпигенетическую регуляцию экспрессии генов в ходе старения и при патологиях – один из наиболее важных аспектов поддержания гомеостаза органов и тканей. Представленный обзор посвящен разнообразию белков­-сиртуинов у человека и модельных животных. Помимо краткого описания основных ферментативных и биологических активностей сиртуинов, рассматривается роль сиртуинов в эпигенетической регуляции структуры хроматина, в том числе в контексте развития нестабильности генома, ассоциированной со старением. Проведен критический анализ работ по исследованию функциональной связи сиртуинов и долголетия, а также влияния сиртуинов на ассоциированные со старением патологические процессы, такие как хроническое воспаление, фиброз и нейровоспаление.

Advances in modern healthcare in developed countries make it possible to extend the human lifespan, which is why maintaining active longevity is becoming increasingly important. After the sirtuin (SIRT) protein family was discovered, it started to be considered as a significant regulator of the physiological processes associated with aging. SIRT has deacetylase, deacylase, and ADP­ribosyltransferase activity and modifies a variety of protein substrates, including chromatin components and regulatory proteins. This multifactorial regulatory system affects many processes: cellular metabolism, mitochondrial functions, epigenetic regulation, DNA repair and more. As is expected, the activity of sirtuin proteins affects the manifestation of classic signs of aging in the body, such as cellular senescence, metabolic disorders, mitochondrial dysfunction, genomic instability, and the disruption of epigenetic regulation. Changes in the SIRT activity in human cells can also be considered a marker of aging and are involved in the genesis of various age­dependent disorders. Additionally, experimental data obtained in animal models, as well as data from population genomic studies, suggest a SIRT effect on life expectancy. At the same time, the diversity of sirtuin functions and biochemical substrates makes it extremely complicated to identify cause­and­effect relationships and the direct role of SIRT in controlling the functional state of the body. However, the SIRT influence on the epigenetic regulation of gene expression during the aging process and the development of disorders is one of the most important aspects of maintaining the homeostasis of organs and tissues. The presented review centers on the diversity of SIRT in humans and model animals. In addition to a brief description of the main SIRT enzymatic and biological activity, the review discusses its role in the epigenetic regulation of chromatin structure, including the context of the development of genome instability associated with aging. Studies on the functional connection between SIRT and longevity, as well as its effect on pathological processes associated with aging, such as chronic inflammation, fibrosis, and neuroinflammation, have been critically analyzed.

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