References

vavilov

Вавиловский журнал генетики и селекции

Vavilov Journal of Genetics and Breeding

2500-3259

Institute of Cytology and Genetics of Siberian Branch of the RAS

10.18699/VJGB-23-60

vavilov-3866

Research Article

ГЕНЕТИКА ЧЕЛОВЕКА

HUMAN GENETICS

Количественные параметры генома человека при старении

Quantifying human genome parameters in aging

https://orcid.org/0000-0001-7355-9882

Волобаев

В. П.

Volobaev

V. P.

Сочи

Sochi

volobaev.vp@gmail.com

https://orcid.org/0000-0003-1882-0667

Кунижева

С. С.

Kunizheva

S. S.

Сочи; Москва

Sochi; Moscow

https://orcid.org/0000-0002-5565-7961

Уральский

Л. И.

Uralsky

L. I.

Сочи; Москва

Sochi; Moscow

https://orcid.org/0009-0002-2228-6276

Куприянова

Д. A.

Kupriyanova

D. A.

Сочи

Sochi

https://orcid.org/0000-0002-0351-8783

Рогаев

Е. И.

Rogaev

E. I.

Сочи; Москва; Шрусбери, США

Sochi; Moscow; Shrewsbury, USA

Научно-технологический университет «Сириус», Научный центр генетики и наук о жизниРоссияSirius University of Science and Technology, Scientific Center for Genetics and Life SciencesRussian Federation

Научно-технологический университет «Сириус», Научный центр генетики и наук о жизни; Институт общей генетики им. Н.И. Вавилова Российской академии наук, отдел геномики и генетики человека; Московский государственный университет им. М.В. Ломоносова, Центр генетики и генетических технологий, биологический факультетРоссияSirius University of Science and Technology, Scientific Center for Genetics and Life Sciences; Vavilov Institute of General Genetics, Russian Academy of Sciences, Department of Genomics and Human Genetics; Lomonosov Moscow State University, Center for Genetics and Genetic Technologies, Faculty of BiologyRussian Federation

Научно-технологический университет «Сириус», Научный центр генетики и наук о жизни; Институт общей генетики им. Н.И. Вавилова Российской академии наук, отдел геномики и генетики человекаРоссияSirius University of Science and Technology, Scientific Center for Genetics and Life Sciences; Vavilov Institute of General Genetics, Russian Academy of Sciences, Department of Genomics and Human GeneticsRussian Federation

Научно-технологический университет «Сириус», Научный центр генетики и наук о жизни; Институт общей генетики им. Н.И. Вавилова Российской академии наук, отдел геномики и генетики человека; Московский государственный университет им. М.В. Ломоносова, Центр генетики и генетических технологий, биологический факультет; Медицинская школа Чан Массачусетского университета, отделение психиатрииРоссияSirius University of Science and Technology, Scientific Center for Genetics and Life Sciences; Vavilov Institute of General Genetics, Russian Academy of Sciences, Department of Genomics and Human Genetics; Lomonosov Moscow State University, Center for Genetics and Genetic Technologies, Faculty of Biology; University of Massachusetts Chan Medical School, Department of PsychiatryRussian Federation

2023

09092023

275495501

2023

Волобаев В.П., Кунижева С.С., Уральский Л.И., Куприянова Д.A., Рогаев Е.И.

Volobaev V.P., Kunizheva S.S., Uralsky L.I., Kupriyanova D.A., Rogaev E.I.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://vavilov.elpub.ru/jour/article/view/3866

Здоровое долголетие человека – глобальная цель мировой системы здравоохранения. В то же время неуклонное старение населения стало серьезным вызовом для систем здравоохранения многих стран мира, в том числе из-за возросшего риска развития многих тяжелых нейродегенеративных заболеваний, включая болезнь Альцгеймера (БА) и болезнь Паркинсона (БП). Определение причин и процессов, влияющих на старение и продолжительность жизни человека, а также выявление механизмов развития возрастных патологий – первостепенная фундаментальная задача, стоящая перед научным сообществом. В настоящее время основные усилия направлены на идентификацию качественных характеристик генома, детерминирующих признак. Вместе с тем при их оценке существует множество проблем, затрудняющих установление ассоциаций. Количественные признаки обременены таковыми проблемами в меньшем объеме, но в большинстве случаев упускаются при проведении современных геномных исследований, посвященных вопросам старения и долголетия. Несмотря на наличие широкого круга возможностей проведения анализа геномных данных по количественным признакам, большинство возможностей не используется, что наряду с недоступностью опубликованных данных ведет к потере этой важной информации. Настоящий обзор посвящен описанию количественных признаков, важных для понимания процесса старения и необходимых для анализа в дальнейших геномных исследованиях, и является рекомендацией для включения описанных признаков в анализ. Рассматривается взаимосвязь количественных характеристик ядерного и митохондриального генома со старением, долголетием и возрастными нейродегенеративными заболеваниями, таких как частота обширных делеций митохондриальной ДНК (mtDNA), время полураспада mtDNA, частота замен A>G в тяжелой цепи mtDNA, количество копий mtDNA, длина теломер, частота соматических мутаций. В целом можно отметить, что есть достаточно серьезные причины полагать, что различные количественные характеристики генома могут быть прямо или косвенно ассоциированы с теми или иными аспектами старения и продолжительности жизни. Но имеющихся данных недостаточно для окончательных выводов и выявления причинно-следственных связей.

Healthy human longevity is a global goal of the world health system. Determining the causes and processes influencing human longevity is the primary fundamental goal facing the scientific community. Currently, the main efforts of the scientific community are aimed at identifying the qualitative characteristics of the genome that determine the trait. At the same time, when evaluating qualitative characteristics, there are many challenges that make it difficult to establish associations. Quantitative traits are burdened with such problems to a lesser extent, but they are largely overlooked in current genomic studies of aging and longevity. Although there is a wide repertoire of quantitative trait analyses based on genomic data, most opportunities are ignored by authors, which, along with the inaccessibility of published data, leads to the loss of this important information. This review focuses on describing quantitative traits important for understanding aging and necessary for analysis in further genomic studies, and recommends the inclusion of the described traits in the analysis. The review considers the relationship between quantitative characteristics of the mitochondrial genome and aging, longevity, and age-related neurodegenerative diseases, such as the frequency of extensive mitochondrial DNA (mtDNA) deletions, mtDNA half-life, the frequency of A>G replacements in the mtDNA heavy chain, the number of mtDNA copies; special attention is paid to the mtDNA methylation sign. A separate section of this review is devoted to the correlation of telomere length parameters with age, as well as the association of telomere length with the amount of mitochondrial DNA. In addition, we consider such a quantitative feature as the rate of accumulation of somatic mutations with aging in relation to the lifespan of living organisms. In general, it may be noted that there are quite serious reasons to suppose that various quantitative characteristics of the genome may be directly or indirectly associated with certain aspects of aging and longevity. At the same time, the available data are clearly insufficient for definitive conclusions and the determination of causal relationships.

количественные параметры геномастарениедолголетиенейродегенеративные заболеванияmtDNAдлина теломерсоматические мутации

genome quantificationaginglongevityneurodegenerative disordersmtDNAtelomere lengthsomatic mutations

This work was supported financially by the Russian Science Foundation under Scientific Project No. 19-75-30039 (R.E.I., K.S.S., U.L.I.) and the Sirius University of Science and Technology under Scientific Project GEN-RND-2019 (V.V.P., K.D.A.).

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