Laboratory of Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Laboratory of Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Ageing Res Rev. 2019 Nov;55:100941. doi: 10.1016/j.arr.2019.100941. Epub 2019 Aug 10.
Senotherapy is an antiageing strategy. It refers to selective killing of senescent cells by senolytic agents, strengthening the activity of immune cells that eliminate senescent cells or alleviating the secretory phenotype (SASP) of senescent cells. As senescent cells accumulate with age and are considered to be at the root of age-related disorders, senotherapy seems to be very promising in improving healthspan. Genetic approaches, which allowed to selectively induce death of senescent cells in transgenic mice, provided proof-of-concept evidence that elimination of senescent cells can be a therapeutic approach for treating many age-related diseases. Translating these results into humans is based on searching for synthetic and natural compounds, which are able to exert such beneficial effects. The major challenge in the field is to show efficacy, safety and tolerability of senotherapy in humans. The question is how these therapeutics can influence senescence of non-dividing post-mitotic cells. Another issue concerns senescence of cancer cells induced during therapy as there is a risk of resumption of senescent cell division that could terminate in cancer renewal. Thus, development of an effective senotherapeutic strategy is also an urgent issue in cancer treatment. Different aspects, both beneficial and potentially detrimental, will be discussed in this review.
衰老细胞治疗是一种抗衰老策略。它是指通过衰老细胞溶解剂选择性地杀死衰老细胞，增强清除衰老细胞的免疫细胞的活性，或减轻衰老细胞的分泌表型（SASP）。随着衰老细胞在体内的积累，衰老细胞被认为是与年龄相关疾病的根源，因此衰老细胞治疗似乎在改善健康寿命方面很有前景。遗传方法允许在转基因小鼠中选择性地诱导衰老细胞死亡，为消除衰老细胞可以成为治疗许多与年龄相关疾病的一种治疗方法提供了概念验证证据。将这些结果转化为人类，依赖于寻找能够发挥这种有益作用的合成和天然化合物。该领域的主要挑战是证明衰老细胞治疗在人类中的疗效、安全性和耐受性。问题是这些疗法如何影响非分裂有丝后细胞的衰老。另一个问题涉及治疗过程中诱导的癌细胞衰老，因为有恢复衰老细胞分裂的风险，这可能导致癌症复发。因此，开发有效的衰老细胞治疗策略也是癌症治疗中的一个紧迫问题。本综述将讨论衰老细胞治疗有益和潜在有害的各个方面。
