Mahoney Sophia A, Bloom Samuel I, Seals Douglas R, Donato Anthony J, Rossman Matthew J, Clayton Zachary S
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
Salk Institute for Biological Studies, La Jolla, CA 90237, USA.
J Cardiovasc Aging. 2025;5(2). doi: 10.20517/jca.2024.31. Epub 2025 Mar 19.
Cardiovascular diseases (CVD) remain the leading cause of death worldwide, with advancing age being the primary, nonmodifiable risk factor. Vascular dysfunction, namely arterial stiffening and endothelial dysfunction, is the key antecedent to the development of clinical CVD with aging. Fundamental aging macro-mechanistic processes that drive vascular aging include excess oxidative stress, chronic inflammation, and declines in the vasodilatory molecule nitric oxide. An important hallmark of aging that contributes to the vascular aging processes is cellular senescence - a stress response characterized by cell cycle arrest and accompanied by the production and secretion of proinflammatory molecules (i.e., the senescence-associated secretory phenotype [SASP]). Excess senescent cells and the SASP have deleterious effects on vascular function and in states of CVD, making it a putative therapeutic target for improving vascular function and preventing or reversing CVD. This review will focus on the role of cellular senescence in age-related vascular dysfunction and CVD. We will examine established and emerging mechanisms underlying cellular senescence-induced vascular dysfunction. We will then discuss groups with impaired vascular function and high cellular senescence burden and examine strategies to reduce or remove excess senescent cells and the SASP in the groups who are likely to benefit most from these therapies. Finally, we will highlight the systemic effects of vascular senescent cell suppression on other tissues and organs, given the integrative role of the vasculature in physiology. Together, this review will underscore the imperative role of cellular senescence in vascular dysfunction and the need for a deeper understanding of the translational use of cellular senescence and SASP targeting therapies in groups with high senescent cell burden.
心血管疾病（CVD）仍然是全球首要的死亡原因，年龄增长是主要的、不可改变的风险因素。血管功能障碍，即动脉僵硬和内皮功能障碍，是随着年龄增长临床CVD发生发展的关键先兆。驱动血管衰老的基本衰老宏观机制过程包括氧化应激过剩、慢性炎症以及血管舒张分子一氧化氮水平下降。导致血管衰老过程的一个重要衰老标志是细胞衰老——一种以细胞周期停滞为特征的应激反应，并伴有促炎分子的产生和分泌（即衰老相关分泌表型 [SASP]）。过多的衰老细胞和SASP对血管功能以及CVD状态具有有害影响，使其成为改善血管功能和预防或逆转CVD的一个假定治疗靶点。本综述将聚焦细胞衰老在与年龄相关的血管功能障碍和CVD中的作用。我们将研究细胞衰老诱导血管功能障碍的既定机制和新出现的机制。然后，我们将讨论血管功能受损且细胞衰老负担高的人群，并研究在可能从这些治疗中获益最大的人群中减少或清除过多衰老细胞和SASP的策略。最后，鉴于血管系统在生理学中的整合作用，我们将强调抑制血管衰老细胞对其他组织和器官的全身影响。总之，本综述将强调细胞衰老在血管功能障碍中的重要作用，以及更深入了解细胞衰老和SASP靶向治疗在衰老细胞负担高的人群中的转化应用的必要性。
