Генетика старения и долголетия

Продолжительность жизни является комплексным количествен­ ным признаком, вносящим определяющий вклад в дарвиновскую приспособленность. Раскрытие генетической природы долгожи­ тельства – фундаментальная проблема эволюции онтогенеза, эво­ люционной генетики и молекулярной геронтологии. В оптимальных условиях существования продолжительность жизни опреде­ляется скоростью старения. В свою очередь, феномен старения состоит из взаимосвязанных процессов, происходящих на орга­низменном, тканевом, клеточном, молекулярно-генетическом уровнях. Они включают дерегуляцию процессов поддержания гомеостаза, метаболических реакций и передачи внутри- и меж­ клеточных сигналов, накопление неспособных к делению клеток, поврежденных органелл и макромолекул, эпигенетические изме­нения и генетическую нестабильность. Задачей настоящего обзора является обобщение имеющихся сведений об основных генетиче­ских детерминантах продолжительности жизни и старения. Рас­смотрены гены и сигнальные каскады, влияющие на скорость старения через регуляцию стресс-ответа, обмена веществ, роста клеток и организма, поддержание целостности генома и протео­ма, качественного и количественного состава митохондрий, вос­палительного ответа, апоптоза и селекции жизнеспособных клеток, а также циркадных ритмов. Перераспределение энергетических ресурсов между процессами роста и самоподдержания жизнеспо­ собности может запустить либо отключить «программу долгожи­ тельства», обеспечивая повышенную устойчивость к стрессам и замедленное старение организма. На основании анализа геро­протекторного потенциала регуляции активности рассматривае­мых генов были выделены возможные подходы для замедления старения и достижения здорового долголетия. К ним отнесены восстановление гетерохроматина; подавление ретротранспози­ций; устранение клеток с анеуплоидией; восстановление кислот­ности лизосом; удлинение теломер; подавление хронического воспаления; устранение перекрестных сшивок белков; элимина­ция сенесцентных клеток; восстановление уровней НАД+; ингиби­рование mTOR, S6K, TGF-β, AT1; контролируемая активация генов «программы долгожительства» FOXO, AMPK, PGC1α, NRF2.

продолжительность жизни, старение, гены долголетия, программа долголетия

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