Lecot Pacome, Alimirah Fatouma, Desprez Pierre-Yves, Campisi Judith, Wiley Christopher
Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
California Pacific Medical Center, 475 Brannan Street, San Francisco, CA 94107, USA.
Br J Cancer. 2016 May 24;114(11):1180-4. doi: 10.1038/bjc.2016.115. Epub 2016 May 3.
Cellular senescence is an established tumour-suppressive mechanism that prevents the proliferation of premalignant cells. However, several lines of evidence show that senescent cells, which often persist in vivo, can also promote tumour progression in addition to other age-related pathologies via the senescence-associated secretory phenotype (SASP). Moreover, new insights suggest the SASP can facilitate tissue repair. Here, we review the beneficial and detrimental roles of senescent cells, highlighting conditions under which the senescence response does and does not promote pathology, particularly cancer. By better understanding the context-dependent effects of cellular senescence, it may be feasible to limit its detrimental properties while preserving its beneficial effects, and develop novel therapeutic strategies to prevent or treat cancer and possibly other age-associated diseases.
细胞衰老作为一种既定的肿瘤抑制机制,可防止癌前细胞的增殖。然而,多项证据表明,衰老细胞虽常留存于体内,但除了通过衰老相关分泌表型(SASP)引发其他与年龄相关的病理变化外,还能促进肿瘤进展。此外,新的研究表明,SASP能够促进组织修复。在此,我们综述了衰老细胞的有益和有害作用,重点阐述了衰老反应促进和不促进病理变化(尤其是癌症)的条件。通过更好地理解细胞衰老的背景依赖性效应,或许可以在保留其有益作用的同时限制其有害特性,并开发出预防或治疗癌症以及其他可能与年龄相关疾病的新型治疗策略。