Роль старения в терапии болезни Альцгеймера

   Введение. Наиболее значимым фактором риска болезни Альцгеймера (БА) является старение, которое способствует нарушению клиренса тау-протеина и амилоида-β (Aβ) белков, сенесценции микроглии, стрессу эндоплазматического ретикулума (ЭР), дисрегуляции липидов и иксайтотоксичности. В обзоре рассматривается, как старение ускоряет патофизиологические механизмы БА, а также оцениваются новые научные (geroscience) подходы, направленные на изучение биологических процессов старения с целью задержки или предотвращения когнитивного снижения.

   Материал и методы. Проведен нарративный обзор литературы за период 2015–2025 гг. с интеграцией данных лонгитюдных исследований, метаанализов и доклинических моделей, изучающих взаимосвязь старения и БА. Поисковые запросы в базах MED-LINE, Embase, Cochrane, Google Scholar и PubMed включали ключевые слова: старение, БА, патология БА, антиэйджинг-стратегии и терапия БА.

   Результаты. На этапе первичного поиска было исключено более 150 исследований, и только 100 работ были отобраны для дальнейшего анализа. После дополнительной проверки были удалены 30 дублирующих исследований. В конечном итоге обзор включил 70 исследований. Большинство из них рассматривали механизмы, связанные со старением — дисфункцию глимфатической системы, нарушение транспорта липидов, связанное с APOE ε4, снижение уровня BDNF и глутамат-опосредованную иксайтотоксичность, а также антиэйджинг-стратегии, включая изменения образа жизни (физическая активность, оптимизация сна, когнитивная активность) и медицинские или биологические терапии БА.

   Заключение. Нацеливание на механизмы старения представляет собой смену парадигмы в профилактике и лечении БА; однако для внедрения геронауки в клиническую практику необходима междисциплинарная работа. Интеграция стратегий образа жизни и фармакологических вмешательств может обеспечить синергетическую нейропротекцию. Будущие исследования должны быть сосредоточены на интегрированных мультимодальных подходах, сочетающих модификацию образа жизни, и биологическими методами лечения. Индивидуализированные стратегии – основанные на генетическом риске (например, статус APOE), сопутствующих заболеваниях и индивидуальных траекториях старения – могут оптимизировать результаты. Для оценки долгосрочной безопасности и эффективности инновационных вмешательств, таких как сенолитики, эпигенетические модуляторы и стволовые клеточные терапии, необходимы крупные длительные клинические исследования. Прогресс в области биомаркеров биологического возраста, машинного обучения и системной биологии может улучшить оценку риска и персонализацию терапии.

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