Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Biogerontology. 2020 Oct;21(5):517-530. doi: 10.1007/s10522-020-09876-w. Epub 2020 Apr 3.
Accumulation of senescent cells in vascular endothelium is known to contribute to vascular aging and increases the risk of developing cardiovascular diseases. The involvement of classical pathways such as p53/p21 and p16/pRB in cellular senescence are well described but there are emerging evidence supporting the increasingly important role of mammalian target of rapamycin (MTOR) as driver of cellular senescence via these pathways or other effector molecules. MicroRNAs (miRNAs) are a highly conserved group of small non-coding RNAs (18-25 nucleotides), instrumental in modulating the expression of target genes associated with various biological and cellular processes including cellular senescence. The inhibition of MTOR activity is predominantly linked to cellular senescence blunting and prolonged lifespan in model organisms. To date, known miRNAs regulating MTOR in endothelial cell senescence remain limited. Herein, this review discusses the roles of MTOR and MTOR-associated miRNAs in regulating endothelial cell senescence, including the crosstalk between MTOR Complex 1 (MTORC1) and cell cycle pathways and the emerging role of MTORC2 in cellular senescence. New insights on how MTOR and miRNAs coordinate underlying molecular mechanisms of endothelial senescence will provide deeper understanding and clarity to the complexity of the regulation of cellular senescence.
衰老细胞在血管内皮中的积累被认为是导致血管老化和增加心血管疾病风险的原因。p53/p21 和 p16/pRB 等经典途径在细胞衰老中的参与已经得到很好的描述，但越来越多的证据支持哺乳动物雷帕霉素靶蛋白 (mTOR) 通过这些途径或其他效应分子作为细胞衰老的驱动因素的作用。microRNAs (miRNAs) 是一组高度保守的小非编码 RNA（18-25 个核苷酸），在调节与各种生物学和细胞过程相关的靶基因表达方面发挥重要作用，包括细胞衰老。抑制 mTOR 活性主要与细胞衰老变钝和模型生物中寿命延长有关。迄今为止，已知调节内皮细胞衰老的 miRNA 仍然有限。本文讨论了 mTOR 和 mTOR 相关 miRNA 在调节内皮细胞衰老中的作用，包括 mTOR 复合物 1 (MTORC1) 和细胞周期途径之间的串扰以及 MTORC2 在细胞衰老中的新兴作用。关于 mTOR 和 miRNAs 如何协调内皮衰老的潜在分子机制的新见解，将为细胞衰老调控的复杂性提供更深入的理解和清晰认识。
