mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-IAT-1938mimmun-1938Research ArticleОБЗОРЫREVIEWSВоспалительное старение как основа возраст-ассоциированной патологииInflammaging as the basis of age-associated diseasesАртемьеваО. В.ArtemyevaO. V.

Артемьева Ольга Владимировна – к.м.н., доцент кафедры иммунологии

101000, Москва, Чистопрудный бульвар, 9, кв. 41. Тел.: 8 (916) 678-92-01.

Artemyeva Olga V. – PhD (Medicine), Associate Professor, Department of Immunology

101000, Moscow, Chistoprudny blvd, 9, apt 41.Phone: 7 (916) 678-92-01.

artemyevaov@yandex.ruГанковскаяЛ. В.GankovskayaL. V.

д.м.н., профессор, заведующая кафедрой иммунологии

Москва

PhD, MD (Medicine), Professor, Head, Department of Immunology

Moscow

lvgan@yandex.ruФГАОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения РФРоссияN. Pirogov Russian National Research Medical UniversityRussian Federation202020052020223419432Copyright © Артемьева О.В., Ганковская Л.В., 20202020Артемьева О.В., Ганковская Л.В.Artemyeva O.V., Gankovskaya L.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1938

Старение представляет собой одно из самых сложных биологических явлений, которое затрагивает все физиологические системы организма человека, в том числе иммунную систему. Под иммуностарением понимают структурные и функциональные изменения как системы адаптивного, так и системы врожденного иммунитета. Одним из проявлений иммуностарения является так называемое воспалительное старение (inflammaging) – возрастное повышение воспалительных медиаторов и развитие воспалительного фенотипа. Важную роль в формировании "inflammaging" отводят хронической стимуляции иммунной системы экзогенными и эндогенными сигналами патогенности и опасности (PAMP и DAMP), среди которых основными являются вирусы, микробиота желудочно-кишечного тракта, свободные радикалы и др. Распознавание PAMP и DAMP осуществляется клетками системы врожденного иммунитета посредством паттерн-распознающих рецепторов (PRR), которые включают Toll-подобные рецепторы (TLR), RIG-I-подобные рецепторы (RLR), NOD-подобные рецепторы (NLR), лектиновые рецепторы. Cтимуляция PRR приводит к активации внутриклеточного сигналинга и усилению экспрессии провоспалительных факторов. PAMP являются наиболее сильными активаторами паттерн-распознающих рецепторов и пусковыми факторами воспаления, DAMP могут активировать те же рецепторы и сигнальные пути, вызывая развитие стерильной воспалительной реакции. NF-kB-сигнальный путь рассматривается в качестве ключевого сигнального пути развития "inflammaging". Стимуляция NLR также приводит к образованию инфламмасомы, одной из функций которой является процессинг провоспалительных цитокинов до биологически активной формы, что является важным фактором формирования провоспалительного фенотипа и развития "inflammaging". "Inflammaging" считается важным фактором риска заболеваемости и смертности среди пожилых людей. Хроническое воспаление лежит в основе патогенеза многих возраст-ассоциированных заболеваний, таких как остеопороз, атеросклероз, болезнь Альцгеймера, болезнь Паркинсона, сахарный диабет 2 типа. Поскольку различные хронические заболевания, связанные с возрастом, напрямую связаны с PAMP- и DAMP-индуцированным TLR или NLRP3-опосредованным воспалительным ответом, эти лиганды и их рецепторы могут рассматриваться в качестве биомаркеров и интервенционных мишеней при возрастной патологии. Несмотря на многочисленные исследования при возраст-ассоциированных патологиях, исследования вклада компонентов врожденного иммунитета при здоровом старении являются недостаточными. Остается неясным, является ли воспалительный фенотип проявлением здорового старения или ассоциирован с развитием возрастной патологии. Дальнейшее изучение механизмов воспалительного старения позволит выявить биомаркеры здорового старения и потенциальные мишени для терапии возраст-ассоциированных заболеваний.

Aging is one of the most complex biological phenomena that affects all human physiological systems, including the immune system. Immunosenescence is understood as structural and functional changes in both adaptive and innate immunity systems. The so-called inflammaging is among manifestations of immune aging. It is an age-related increase in inflammatory mediators and development of an inflammatory phenotype. An important role in development of inflammaging is assigned to chronic stimulation of immune system by exogenous and endogenous danger signals (pathogen-associated molecular pattern, PAMP and damage-associated molecular pattern, DAMP), which include viruses, microbiota of the gastrointestinal tract, free radicals, etc. PAMP and DAMP are recognized by the innate immunity system cells through the pattern recognition receptors (PRR), e.g., Toll-like receptors (TLR), RIG-I-like receptors (RLR), NODlike receptors (NLR), lectin receptors. Stimulation of PRR leads to activation of intracellular signaling and increased expression of pro-inflammatory factors. PAMPs are the most powerful activators of PRR and inflammation triggers; DAMPs can activate the same receptors and signaling pathways, causing the development of a sterile inflammatory response. The NF-kB signaling pathway is considered as a key signaling pathway for inflammaging. NLR stimulation also leads to formation of inflammasome. Its function is to transform the pro-inflammatory cytokines to a biologically active form, which is an important for the formation of a pro-inflammatory phenotype and development of inflammaging. This process is considered an important risk factor for morbidity and mortality among older people. Chronic inflammation underlies pathogenesis of many age-related diseases, such as osteoporosis, atherosclerosis, Alzheimer’s disease, Parkinson’s disease, type 2 diabetes. Various chronic diseases associated with age are directly related to PAMP and DAMP-induced TLR or NLRP3-mediated inflammatory response. Hence, these ligands and their receptors can be suggested as biomarkers and interventional targets for age-related disorders. Despite numerous studies in age-associated pathology, there are only few works on the contribution of innate immunity in healthy aging. It remains unclear whether the inflammatory phenotype is a manifestation of healthy aging, or it is associated with development of age-related pathology. Further study of the mechanisms of inflammatory aging will reveal biomarkers of healthy aging and potential targets for the treatment of age-associated diseases.

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