Atlante Sandra, Gottardi Zamperla Michela, Cis Luca, Farsetti Antonella, Gaetano Carlo
Laboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, 27100, Pavia, Italy; Institute for Systems Analysis and Computer Science, National Research Council (CNR)- IASI, 00185, Rome, Italy.
Laboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, 27100, Pavia, Italy.
Eur J Intern Med. 2025 Jul 15. doi: 10.1016/j.ejim.2025.07.009.
Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, with aging as a critical risk factor. Cellular senescence, marked by irreversible cell cycle arrest and a pro-inflammatory secretory phenotype, drives age-related cardiovascular pathologies, including vascular dysfunction, atherosclerosis, cardiac fibrosis, and metabolic disturbances. Senolytics-agents that selectively eliminate senescent cells-represent a promising therapeutic strategy. This review explores the role of senescence in CVD and evaluates senolytics potential to improve vascular function, reduce fibrosis, and address CVD-related metabolic and immune dysfunctions. Preclinical studies have shown promising results in improving heart function, particularly in the treatment of heart failure, in post-myocardial infarction recovery, and cardiac transplantation. The interplay between senescence and immunosenescence in CVD is also examined, highlighting the potential of senolytics to rejuvenate immune responses and attenuate chronic inflammation. Furthermore, the review discusses the role of senolytics in addressing metabolic syndrome, a significant contributor to CVD, by alleviating systemic inflammation and insulin resistance. While clinical data remain limited, early-phase trials and strong preclinical evidence provide a compelling rationale for further investigating senolytics in cardiovascular contexts. In this light, the review concludes by emphasizing the challenges and the need for extended preclinical and clinical studies to establish the efficacy, safety, dose, and long-term effects of senolytics and to exploit them as a transformative approach in cardiovascular medicine.
心血管疾病（CVD）仍然是发病和死亡的主要原因，衰老作为一个关键风险因素。细胞衰老以不可逆的细胞周期停滞和促炎分泌表型为特征，驱动与年龄相关的心血管病理变化，包括血管功能障碍、动脉粥样硬化、心脏纤维化和代谢紊乱。衰老细胞溶解剂——选择性清除衰老细胞的药物——代表了一种有前景的治疗策略。本综述探讨衰老在心血管疾病中的作用，并评估衰老细胞溶解剂在改善血管功能、减少纤维化以及解决与心血管疾病相关的代谢和免疫功能障碍方面的潜力。临床前研究在改善心脏功能方面已显示出有前景的结果，特别是在心力衰竭治疗、心肌梗死后恢复以及心脏移植方面。还研究了心血管疾病中衰老与免疫衰老之间的相互作用，强调了衰老细胞溶解剂恢复免疫反应和减轻慢性炎症的潜力。此外，本综述讨论了衰老细胞溶解剂通过减轻全身炎症和胰岛素抵抗在解决代谢综合征（心血管疾病的一个重要促成因素）方面的作用。虽然临床数据仍然有限，但早期试验和有力的临床前证据为在心血管领域进一步研究衰老细胞溶解剂提供了令人信服的理由。有鉴于此，本综述最后强调了挑战以及进行扩展的临床前和临床研究的必要性，以确定衰老细胞溶解剂的疗效、安全性、剂量和长期影响，并将它们作为心血管医学中的一种变革性方法加以利用。
