Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Intensive Care Unit, "Sotiria" Thoracic Diseases General Hospital, Athens, Greece.
Physiol Rev. 2023 Jan 1;103(1):609-647. doi: 10.1152/physrev.00007.2022. Epub 2022 Sep 1.
Cardiovascular diseases (CVDs) constitute the prime cause of global mortality, with an immense impact on patient quality of life and disability. Clinical evidence has revealed a strong connection between cellular senescence and worse cardiac outcomes in the majority of CVDs concerning both ischemic and nonischemic cardiomyopathies. Cellular senescence is characterized by cell cycle arrest accompanied by alterations in several metabolic pathways, resulting in morphological and functional changes. Metabolic rewiring of senescent cells results in marked paracrine activity, through a unique secretome, often exerting deleterious effects on neighboring cells. Here, we recapitulate the hallmarks and key molecular pathways involved in cellular senescence in the cardiac context and summarize the different roles of senescence in the majority of CVDs. In the last few years, the possibility of eliminating senescent cells in various pathological conditions has been increasingly explored, giving rise to the field of senotherapeutics. Therefore, we additionally attempt to clarify the current state of this field with a focus on cardiac senescence and discuss the potential of implementing senolytics as a treatment option in heart disease.
心血管疾病（CVDs）是全球死亡的主要原因，对患者的生活质量和残疾状况有着巨大影响。临床证据表明，在大多数与缺血性和非缺血性心肌病相关的 CVDs 中，细胞衰老与更差的心脏预后之间存在很强的关联。细胞衰老的特征是细胞周期停滞，伴随着几种代谢途径的改变，导致形态和功能的变化。衰老细胞的代谢重编程导致独特的分泌组产生明显的旁分泌活性，常常对邻近细胞产生有害影响。在这里，我们概括了心脏环境中细胞衰老涉及的特征和关键分子途径，并总结了衰老在大多数 CVDs 中的不同作用。在过去的几年中，人们越来越多地探索在各种病理条件下消除衰老细胞的可能性，从而产生了衰老治疗学这一领域。因此，我们还试图通过关注心脏衰老来阐明该领域的现状，并讨论使用衰老细胞清除剂作为心脏病治疗选择的潜力。
