Cuollo Lorenzo, Antonangeli Fabrizio, Santoni Angela, Soriani Alessandra
Department of Molecular Medicine, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy.
Center for Life Nano Science, Sapienza, Istituto Italiano di Tecnologia, 00161 Rome, Italy.
Biology (Basel). 2020 Dec 21;9(12):485. doi: 10.3390/biology9120485.
Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called "senomorphics". In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.
细胞衰老代表一种强大的肿瘤保护机制，可阻止应激细胞或癌前细胞的增殖。然而，这种稳定的增殖停滞状态伴随着衰老相关分泌表型（SASP），这需要在组织微环境中大量分泌促炎信号，并导致与年龄相关的病症，矛盾的是，其中包括癌症。新型治疗策略旨在使用衰老细胞溶解剂消除衰老细胞，或使用所谓的“衰老形态调节剂”在不杀死衰老细胞的情况下消除SASP。此外，最近的研究表明，通过基因或药物干预改变分泌蛋白质组的组成是可能的。目的不是放弃SASP强大的免疫刺激特性，而是学会调节它以对抗癌症和其他与年龄相关的疾病。本综述描述了调节SASP的主要分子机制，并报告了废除或调节SASP可行性的证据，讨论了这两种策略可能产生的影响。
