Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1783410.15789/2220-7619-IOV-17834REVIEWSОБЗОРЫReview ArticleImpact of viruses and retrotransposons on genetic instability and agingВлияние вирусов и ретротранспозонов на генетическую нестабильность и старение организмаLysakovaElena V.ЛысаковаЕлена Васильевна
Russian Federation

PhD Student, Junior Researcher, Division of Immunobiology and Biomedicine

аспирант, младший научный сотрудник, направление «Иммунобиология и биомедицина»

helena.llysakova@mail.ruBurakMarina Y.БуракМарина Юрьевна
Russian Federation

Мaster’s degree Student

магистрант

marina.burak188@mail.ruNavrotskyMaxim B.НавроцкийМаксим Борисович
Russian Federation

PhD (Pharmacy), Head of the Medical Chemistry Group, Division of Medical Biotechnology

к.ф.н., руководитель группы «Медицинская химия», направление «Медицинская биотехнология»

navrotskij.mb@talantiuspeh.ruRybtsovStanislav A.РыбцовСтанислав Александрович
Russian Federation

PhD (Biology), Head of the Resource Center for Cell Technologies and Immunology

к.б.н., руководитель ресурсного центра клеточных технологий и иммунологии

rybtsov.sa@talantiuspeh.ruSirius University of Science and TechnologyАНОО ВО Научно-технологический университет «Сириус»22042025150920251534464640612202423032025Copyright ©; 2025, Lysakova E.V., Burak M.Y., Navrotsky M.B., Rybtsov S.A.Copyright ©; 2025, Лысакова Е.В., Бурак М.Ю., Навроцкий М.Б., Рыбцов С.А.2025Lysakova E.V., Burak M.Y., Navrotsky M.B., Rybtsov S.A.Лысакова Е.В., Бурак М.Ю., Навроцкий М.Б., Рыбцов С.А.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/17834

Preventive medicine holds significant promise for delaying and even preventing dangerous age-related pathologies. Advances in vaccine development, new preventive medications, cardiovascular implants and early diagnostic tools has increased life expectancy both in Russia and worldwide. Age-dependent genetic instability results in increased risk of developing a number of age-associated diseases. One consequence of this instability is the accumulation of senescent cells across tissues. Senescent cells lose functional activity, replacing normal cells, and are characterized by the secretion of proinflammatory cytokines, creating a chronic inflammatory background, which is the main characteristic of aging. Genetic instability is associated with higher activity of endogenous retroviruses, retrotransposons. Additionally, exogenic viruses and bacteria are able to damage cell genetic apparatus and induce disrupted transcription, translation and repair. The review discusses new approaches aimed at reducing the risk of age-related diseases by controlling genetic instability and viral infections, as well as mechanisms regulating genetic stability. Among the repercussions of disrupting such mechanisms are the development of proliferative, neurodegenerative diseases, cellular senescence and their contribution to chronic inflammation. Antiviral medications and compounds that suppress the activity of endogenous reverse transcriptases are proposed as promising preventive agents for suppressing age-related genetic instability. Although such substances are already used in the clinic to control human immunodeficiency virus, there are currently no medications suitable for long-term use without significant side effects. In this regard, it is primarily important to develop new generation medications that could be used as preventive agents and would meet efficacy and safety requirements, with minimal side effects. The review also explores other promising approaches such as senolytics (agents that selectively eliminate senescent cells) and senomorphics (substances that suppress proinflammatory in prevention of age-associated pathologies. Another perspective method for preventing genetic instability and accumulation of senescent cells is a search for highly specific targets and the development of immunization approaches that allow immune system to remove damaged and senescent cells with increased genetic instability. The proposed approaches can prolong health span and reduce the burden on healthcare system.

Профилактическая медицина имеет многообещающий потенциал для отдаления и даже предотвращения развития опасных патологий, связанных с возрастом. Разработка новых методов вакцинации, новых профилактических препаратов, сердечно-сосудистых имплантов и методов ранней диагностики увеличила продолжительность жизни как в России, так и во всем мире. Повышенный риск развития ряда возраст-ассоциированных заболеваний может быть связан с нарастающей с возрастом генетической нестабильностью и, как результат, накоплением сенесцентных клеток во всех тканях организма. Такие клетки теряют функциональную активность, замещая нормальные клетки, и характеризуются секрецией провоспалительных цитокинов, создавая хронический воспалительный фон, характерный для старения. Возрастание генетической нестабильности связано с увеличением активности эндогенных вирусов и ретротранспозонов, а также с инфицированием рядом вирусов и бактерий, в результате чего происходит повреждение генетического аппарата клетки, нарушение транскрипции, трансляции и репарации. В обзоре обсуждаются новые подходы к профилактике, связанные с контролем генетической нестабильности и вирусных инфекций, повышающих риск возраст-ассоциированных патологий. Обсуждаются причины генетической нестабильности, механизмы контроля и сопутствующие патологии, включая развитие пролиферативных, нейродегенеративных заболеваний, старение клеток и их вклад в хроническое воспаление. В качестве перспективных профилактических средств подавления возраст-зависимой генетической нестабильности предлагаются противовирусные препараты и препараты, подавляющие активность эндогенных обратных транскриптаз. Хотя такие препараты уже используются в клинике для контроля вируса иммунодефицита человека, в настоящее время не существует препаратов, которые возможно принимать на постоянной основе без серьезных побочных эффектов. В связи с этим особенно важным является разработка препаратов нового поколения, которые могли бы использоваться как профилактические средства и отвечали бы требованиям эффективности и безопасности, обладая минимальными побочными эффектами. Как перспективное направление в профилактике возраст-ассоциированных патологий обсуждается разработка эффективных и безопасных субстанций, которые способны удалять сенесцентные клетки (сенолитики) либо блокировать секрецию провоспалительных факторов (сеноморфиков), поскольку эти провоспалительные факторы повышают риск развития пролиферативных, нейродегенеративных, аутоиммунных заболеваний. Другим возможным методом профилактики генетической нестабильности и накопления сенесцентных клеток является поиск высокоспецифичных мишеней и разработка методов иммунизации, позволяющих иммунной системе самостоятельно удалить клетки с повышенной генетической нестабильностью. Применяемые в совокупности, предлагаемые подходы способны продлить активный возраст и снизить нагрузку на систему здравоохранения.

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