MRC London Institute of Medical Sciences (LMS), London, UK.
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, UK.
FEBS J. 2023 Mar;290(5):1235-1255. doi: 10.1111/febs.16351. Epub 2022 Jan 25.
Cellular senescence within the cardiovascular system has, until recently, been understudied and unappreciated as a factor in the development of age-related cardiovascular diseases such as heart failure, myocardial infarction and atherosclerosis. This is in part due to challenges with defining senescence within post-mitotic cells such as cardiomyocytes. However, recent evidence has demonstrated senescent-like changes, including a senescence-associated secretory phenotype (SASP), in cardiomyocytes in response to ageing and cell stress. Other replicating cells, including fibroblasts and vascular smooth muscle cells, within the cardiovascular system have also been shown to undergo senescence and contribute to disease pathogenesis. These findings coupled with the emergence of senolytic therapies, to target and eliminate senescent cells, have provided fascinating new avenues for management of several age-related cardiovascular diseases with high prevalence. In this review, we discuss the role of senescent cells within the cardiovascular system and highlight the contribution of senescence cells to common cardiovascular diseases. We discuss the emerging role for senolytics in cardiovascular disease management while highlighting important aspects of senescence biology which must be clarified before the potential of senolytics can be fully realized.
心血管系统中的细胞衰老,直到最近,作为与年龄相关的心血管疾病(如心力衰竭、心肌梗死和动脉粥样硬化)发展相关的一个因素,其研究还不够深入,也没有得到充分认识。这在一定程度上是由于在有丝分裂后细胞(如心肌细胞)中定义衰老所面临的挑战。然而,最近的证据表明,心肌细胞在衰老和细胞应激时会发生类似衰老的变化,包括衰老相关分泌表型(SASP)。心血管系统中的其他复制细胞,包括成纤维细胞和血管平滑肌细胞,也被证明会发生衰老,并有助于疾病的发病机制。这些发现,加上针对衰老细胞的选择性清除疗法(即 senolytic 疗法)的出现,为管理几种具有高患病率的与年龄相关的心血管疾病提供了迷人的新途径。在这篇综述中,我们讨论了衰老细胞在心血管系统中的作用,并强调了衰老细胞对常见心血管疾病的贡献。我们讨论了 senolytic 疗法在心血管疾病管理中的新兴作用,同时强调了在充分发挥 senolytic 疗法的潜力之前,必须阐明衰老生物学的一些重要方面。