Kunizheva S S, Volobaev V P, Plotnikova M Yu, Kupriyanova D A, Kuznetsova I L, Tyazhelova T V, Rogaev E I
Center for Genetics and Life Sciences, Sirius University of Science and Technology, 354340 Sochi, Russia.
Moscow State University, 119234 Moscow, Russia.
Russ J Genet. 2022;58(12):1427-1443. doi: 10.1134/S1022795422120067. Epub 2022 Dec 28.
Aging is a natural process of extinction of the body and the main aspect that determines the life expectancy for individuals who have survived to the post-reproductive period. The process of aging is accompanied by certain physiological, immune, and metabolic changes in the body, as well as the development of age-related diseases. The contribution of genetic factors to human life expectancy is estimated at about 25-30%. Despite the success in identifying genes and metabolic pathways that may be involved in the life extension process in model organisms, the key question remains to what extent these data can be extrapolated to humans, for example, because of the complexity of its biological and sociocultural systems, as well as possible species differences in life expectancy and causes of mortality. New molecular genetic methods have significantly expanded the possibilities for searching for genetic factors of human life expectancy and identifying metabolic pathways of aging, the interaction of genes and transcription factors, the regulation of gene expression at the level of transcription, and epigenetic modifications. The review presents the latest research and current strategies for studying the genetic basis of human aging and longevity: the study of individual candidate genes in genetic population studies, variations identified by the GWAS method, immunogenetic differences in aging, and genomic studies to identify factors of "healthy aging." Understanding the mechanisms of the interaction between factors affecting the life expectancy and the possibility of their regulation can become the basis for developing comprehensive measures to achieve healthy longevity.
The online version contains supplementary material available at 10.1134/S1022795422120067.
衰老乃是身体机能衰退的自然过程,也是决定已步入生殖后期个体预期寿命的主要因素。衰老过程伴随着身体特定的生理、免疫和代谢变化,以及与年龄相关疾病的发展。遗传因素对人类预期寿命的贡献估计约为25% - 30%。尽管在识别可能参与模式生物寿命延长过程的基因和代谢途径方面取得了成功,但关键问题仍然是,由于人类生物和社会文化系统的复杂性,以及预期寿命和死亡原因可能存在的物种差异,这些数据能在多大程度上外推至人类。新的分子遗传学方法显著扩展了寻找人类预期寿命遗传因素以及识别衰老代谢途径、基因与转录因子相互作用、转录水平基因表达调控和表观遗传修饰的可能性。本综述介绍了研究人类衰老和长寿遗传基础的最新研究及当前策略:在遗传群体研究中对单个候选基因的研究、通过全基因组关联研究(GWAS)方法识别的变异、衰老过程中的免疫遗传差异,以及旨在识别“健康衰老”因素的基因组研究。理解影响预期寿命的因素之间的相互作用机制及其调控可能性,可为制定实现健康长寿的综合措施奠定基础。
网络版包含可在10.1134/S1022795422120067获取的补充材料。