Loaiza Natalia, Demaria Marco
University Medical Center Groningen (UMCG), Groningen, The Netherlands.
University Medical Center Groningen (UMCG), Groningen, The Netherlands; European Research Institute for the Biology of Aging (ERIBA), Groningen, The Netherlands.
Biochim Biophys Acta. 2016 Apr;1865(2):155-67. doi: 10.1016/j.bbcan.2016.01.007. Epub 2016 Feb 2.
The senescence response is a potent tumor suppressor mechanism characterized by an irreversible growth arrest in response to potentially oncogenic signals to prevent the proliferation of damaged cells. Late in life, some of the features of senescent cells seem to mediate the development of age-related pathologies, including cancer. In the present review, we present a summary of the current knowledge regarding the causes, effector pathways and cellular features of senescence. We also discuss how the senescence response, initially a tumor suppressor mechanism, turns into a tumor promoter apparently as a consequence of aging. We argue that three age-related phenomena--senescence-associated secretory phenotype (SASP) dysregulation, decline in the immune system function and genomic instability--could contribute, independently or synergistically, to deteriorate the efficacy of the senescence response in stopping cancer. As a consequence, senescent cells could be considered premalignant cells, and targeting senescent cells could be a preventive and therapeutic strategy against cancer.
衰老反应是一种强大的肿瘤抑制机制，其特征是对潜在致癌信号做出不可逆的生长停滞反应，以防止受损细胞增殖。在生命后期，衰老细胞的一些特征似乎介导了包括癌症在内的与年龄相关的病理发展。在本综述中，我们总结了目前关于衰老的原因、效应途径和细胞特征的知识。我们还讨论了衰老反应最初作为一种肿瘤抑制机制，如何显然由于衰老而转变为肿瘤促进机制。我们认为，三种与年龄相关的现象——衰老相关分泌表型（SASP）失调、免疫系统功能下降和基因组不稳定——可能独立或协同作用，导致衰老反应阻止癌症的功效下降。因此，衰老细胞可被视为癌前细胞，靶向衰老细胞可能是一种预防和治疗癌症的策略。
