International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic.
International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic; Division of Medicine, University College London, London, UK; Research Institute of the Medical University of Varna, Varna, Bulgaria.
Lancet Healthy Longev. 2022 Jan;3(1):e67-e77. doi: 10.1016/S2666-7568(21)00300-7.
Cellular senescence is a major contributor to age-related diseases in humans; however, it also has a beneficial role in physiological and pathological processes, including wound healing, host immunity, and tumour suppression. Reducing the burden of cell senescence in animal models of cardiometabolic disorders, inflammatory conditions, neurodegenerative diseases, and cancer using pharmaceutical approaches that selectively target senescent cells (ie, senolytics) or that suppress senescence-associated secretory phenotype (ie, senomorphics) holds great promise for the management of chronic age-associated conditions. Although studies have provided evidence that senolytics or senomorphics are effective at decreasing the number of senescent cells in humans, the short-term and long-term side-effects of these therapies are largely unknown. In this Review, we systematically discuss the senolytics and senomorphics that have been investigated in clinical trials or have been used off-label, presenting their various adverse effects. Despite the potential of senotherapeutics to transform anti-ageing medicine, a cautionary approach regarding unwanted dose-dependent side-effects should be adopted.
细胞衰老（cellular senescence）是导致人类与年龄相关疾病的主要因素；然而，它在生理和病理过程中也具有有益的作用，包括伤口愈合、宿主免疫和肿瘤抑制。使用选择性靶向衰老细胞（即衰老细胞清除剂）或抑制衰老相关分泌表型（即衰老模拟物）的药物方法来减轻代谢紊乱、炎症、神经退行性疾病和癌症等动物模型中的细胞衰老负担，对于慢性与年龄相关疾病的管理具有巨大的应用前景。尽管研究已经提供了证据表明衰老细胞清除剂或衰老模拟物能够有效地减少人类衰老细胞的数量，但这些疗法的短期和长期副作用在很大程度上尚不清楚。在这篇综述中，我们系统地讨论了已经在临床试验中进行了研究或被非适应证使用的衰老细胞清除剂和衰老模拟物，并介绍了它们的各种不良反应。尽管衰老治疗有潜力改变抗衰老医学，但对于不必要的、剂量依赖性的副作用，应该采取谨慎的方法。
