McHugh Domhnall, Durán Imanol, Gil Jesús
Senescence Group, MRC Laboratory of Medical Sciences (LMS), London, UK.
Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK.
Nat Rev Drug Discov. 2025 Jan;24(1):57-71. doi: 10.1038/s41573-024-01074-4. Epub 2024 Nov 15.
Cellular senescence is a stress response that restrains the growth of aged, damaged or abnormal cells. Thus, senescence has a crucial role in development, tissue maintenance and cancer prevention. However, lingering senescent cells fuel chronic inflammation through the acquisition of a senescence-associated secretory phenotype (SASP), which contributes to cancer and age-related tissue dysfunction. Recent progress in understanding senescence has spurred interest in the development of approaches to target senescent cells, known as senotherapies. In this Review, we evaluate the status of various types of senotherapies, including senolytics that eliminate senescent cells, senomorphics that suppress the SASP, interventions that mitigate senescence and strategies that harness the immune system to clear senescent cells. We also summarize how these approaches can be combined with cancer therapies, and we discuss the challenges and opportunities in moving senotherapies into clinical practice. Such therapies have the potential to address root causes of age-related diseases and thus open new avenues for preventive therapies and treating multimorbidities.
细胞衰老一种应激反应,可抑制衰老、受损或异常细胞的生长。因此,衰老在发育、组织维持和癌症预防中起着至关重要的作用。然而,持续存在的衰老细胞通过获得衰老相关分泌表型(SASP)来加剧慢性炎症,这会导致癌症和与年龄相关的组织功能障碍。在理解衰老方面的最新进展激发了人们对开发靶向衰老细胞方法(即衰老疗法)的兴趣。在本综述中,我们评估了各种类型衰老疗法的现状,包括消除衰老细胞的衰老溶解疗法、抑制SASP的衰老形态疗法、减轻衰老的干预措施以及利用免疫系统清除衰老细胞的策略。我们还总结了这些方法如何与癌症疗法相结合,并讨论了将衰老疗法应用于临床实践所面临的挑战和机遇。此类疗法有可能解决与年龄相关疾病的根本原因,从而为预防性治疗和治疗多种疾病开辟新途径。