Department of Animal and Human Physiology, Faculty of Biology, Sofia University 'St. Kliment Ohridski', Sofia 1504, Bulgaria.
Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, Skopje 1000, North Macedonia.
Mech Ageing Dev. 2024 Aug;220:111943. doi: 10.1016/j.mad.2024.111943. Epub 2024 May 17.
This review focuses on the vital function that SIRT1 and other sirtuins play in promoting cellular senescence in vascular smooth muscle cells, which is a key element in the pathogenesis of vascular aging and associated cardiovascular diseases. Vascular aging is a gradual process caused by the accumulation of senescent cells, which results in increased vascular remodeling, stiffness, and diminished angiogenic ability. Such physiological alterations are characterized by a complex interplay of environmental and genetic variables, including oxidative stress and telomere attrition, which affect gene expression patterns and trigger cell growth arrest. SIRT1 has been highlighted for its potential to reduce cellular senescence through modulation of multiple signaling cascades, particularly the endothelial nitric oxide (eNOS)/NO signaling pathway. It also modulates cell cycle through p53 inactivation and suppresses NF-κB mediated expression of adhesive molecules at the vascular level. The study also examines the therapeutic potential of sirtuin modulation in vascular health, identifying SIRT1 and its sirtuin counterparts as potential targets for reducing vascular aging. This study sheds light on the molecular basis of vascular aging and the beneficial effects of sirtuins, paving the way for the development of tailored therapies aimed at enhancing vascular health and prolonging life.
本综述聚焦于 SIRT1 和其他 Sirtuins 在促进血管平滑肌细胞衰老中的重要作用,这是血管老化和相关心血管疾病发病机制中的关键因素。血管老化是由衰老细胞积累引起的一个渐进过程,导致血管重塑增加、僵硬和血管生成能力下降。这种生理变化的特点是环境和遗传变量的复杂相互作用,包括氧化应激和端粒磨损,它们影响基因表达模式并触发细胞生长停滞。SIRT1 因其通过调节多个信号通路,特别是内皮型一氧化氮合酶 (eNOS)/NO 信号通路,减少细胞衰老的潜力而备受关注。它还通过抑制 p53 失活和抑制 NF-κB 介导的黏附分子在血管水平的表达来调节细胞周期。该研究还探讨了 Sirtuin 调节在血管健康中的治疗潜力,确定 SIRT1 和其 Sirtuin 对应物是减少血管老化的潜在靶点。这项研究揭示了血管老化的分子基础和 Sirtuins 的有益作用,为开发旨在增强血管健康和延长寿命的靶向治疗铺平了道路。