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小 RNA 生物发生蛋白对衰老、长寿和与年龄相关疾病的关键影响。

The critical impacts of small RNA biogenesis proteins on aging, longevity and age-related diseases.

机构信息

Laboratory of Geroprotective and Radioprotective Technologies, Institute of Biology, Komi Science Centre, Ural Branch, Russian Academy of Sciences, 28 Kommunisticheskaya St., 167982, Syktyvkar, Russian Federation.

Laboratory of Geroprotective and Radioprotective Technologies, Institute of Biology, Komi Science Centre, Ural Branch, Russian Academy of Sciences, 28 Kommunisticheskaya St., 167982, Syktyvkar, Russian Federation; Pitirim Sorokin Syktyvkar State University, 55 Oktyabrsky Prosp., 167001, Syktyvkar, Russian Federation.

出版信息

Ageing Res Rev. 2020 Sep;62:101087. doi: 10.1016/j.arr.2020.101087. Epub 2020 Jun 1.

Abstract

Small RNAs and enzymes that provide their biogenesis and functioning are involved in the organism development and coordination of biological processes, including metabolism, maintaining genome integrity, immune and stress responses. In this review, we focused on the role of small RNA biogenesis proteins in determining the aging and longevity of animals and human. A number of studies have revealed that changes in expression profiles of key enzymes, in particular proteins of the Drosha, Dicer and Argonaute families, are associated with the aging process, as well as with some age-related diseases and progeroid syndromes. Down-regulation of small RNA biogenesis proteins leads to global alterations in the expression of regulatory RNAs, disruption of key molecular, cellular and systemic processes, which leads to a lifespan shortening. In contrast, overexpression of Dicer prolongs lifespan and improves cellular defense. Additionally, the role of small RNA biogenesis proteins in the pathogenesis of age-related diseases, including cancer, inflammaging, neurodegeneration, cardiovascular, metabolic and immune disorders, has been conclusively evidenced. Recent advances in biomedicine allow using these proteins as diagnostic and prognostic biomarkers and therapeutic targets.

摘要

小 RNA 及其生物发生和功能所需的酶参与了生物体的发育和生物过程的协调,包括代谢、基因组完整性的维持、免疫和应激反应。在这篇综述中,我们重点介绍了小 RNA 生物发生蛋白在决定动物和人类衰老和长寿中的作用。许多研究表明,关键酶,特别是 Drosha、Dicer 和 Argonaute 家族蛋白的表达谱的变化与衰老过程以及一些与年龄相关的疾病和早衰综合征有关。小 RNA 生物发生蛋白的下调导致调节性 RNA 的表达发生全局改变,破坏关键的分子、细胞和系统过程,从而导致寿命缩短。相比之下,Dicer 的过表达延长了寿命并增强了细胞防御。此外,小 RNA 生物发生蛋白在与年龄相关的疾病(包括癌症、炎症衰老、神经退行性变、心血管、代谢和免疫紊乱)发病机制中的作用已得到明确证实。生物医学的最新进展允许将这些蛋白质用作诊断和预后生物标志物以及治疗靶标。

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