vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ16.171vavilov-695Research ArticleГенетика развития. ОБЗОРDevelopmental genetics. REVIEWГенетика старения и долголетияGenetics of aging and longevityМоскалевА. А.MoskalevA. A.

Сыктывкар;

Сыктывкар;

Долгопрудный;

Москва

Syktyvkar;

Syktyvkar;

Dolgoprudny;

Moscow

amoskalev@list.ruПрошкинаЕ. Н.ProshkinaE. N.

Сыктывкар

Syktyvkar

БелыйА. А.BelyiA. A.

Сыктывкар

Syktyvkar

СоловьевИ. А.SolovyevI. A.

Сыктывкар

Syktyvkar

Федеральное государственное бюджетное учреждение науки Институт биологии Коми научного центра Уральского отделения Российской академии наук; Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования «Сыктывкарский государственный университет им. Питирима Сорокина»; Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования «Московский физико-технический институт (государственный университет)»; Федеральное государственное бюджетное учреждение науки Институт общей генетики им. Н.И. Вавилова Российской академии наукРоссияInstitute of Biology Komi SC UrB RAS; Syktyvkar State University; Moscow Institute of Physics and Technology; Vavilov Institute of General Genetics RASRussian FederationФедеральное государственное бюджетное учреждение науки Институт биологии Коми научного центра Уральского отделения Российской академии наук; Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования «Сыктывкарский государственный университет им. Питирима Сорокина»РоссияInstitute of Biology Komi SC UrB RAS; Syktyvkar State UniversityRussian Federation201625092016204426440Copyright © Москалев А.А., Прошкина Е.Н., Белый А.А., Соловьев И.А., 20162016Москалев А.А., Прошкина Е.Н., Белый А.А., Соловьев И.А.Moskalev A.A., Proshkina E.N., Belyi A.A., Solovyev I.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/695

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.

Lifespan is a complex quantitative characteristic that makes a significant contribution to the Darwinian adaptiveness. The disclosure of the genetic structure of longevity is a fundamental problem of the evolution of ontogeny, evolutionary genetics and molecular gerontology. Under optimal conditions, the lifespan is determined by the aging rate. The aging process is made up of interrelated processes that take place at the organismal, tissue, cellular, molecular and genetic levels. These include deregulation processes of homeostasis maintenance, metabolic reactions and sending intra- and intercellular signals, accumulation of senescent cells, damaged organelles and macromolecules, epigenetic changes and genetic instability. The objective of this review is to summarize the available information about underlying genetic determinants of longevity and aging. Genes and signaling pathways that regulate stress response, metabolism, growth of cells and organism, maintaining of genome and proteome integrity, qualitative and quantitative mitochondria composition, inflammatory response, apoptosis and selection of viable cells, as well as circadian rhythms were considered. The redistribution of energy resources from one pathway to the other can induce or inhibit the ”longevity program”, providing increased vitality and aging slowdown. Based on the analysis of geroprotective potential of examined genes’ regulation, main targets have been identified to slowdown aging and achieve healthy longevity. These trends include heterochromatin recovery, retrotransposition suppression, aneuploidy elimination; restoring the acidity of lysosomes; telomere elongation; suppression of chronic inflammation; elimination of protein cross-links; elimination of senescent cells; recovery of NAD+ levels; inhibition of mTOR, S6K, TGF-β, AT1; controlled activation of the ”longevity program” genes FOXO, AMPK, PGC1α, NRF2.

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