Department of Physiology and Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, USA.
Crit Rev Oncol Hematol. 2011 Aug;79(2):189-95. doi: 10.1016/j.critrevonc.2010.07.011. Epub 2010 Aug 11.
Aging is manifest in a variety of changes over time, including changes at the cellular level. Cellular aging acts primarily as a tumor suppressor mechanism, but also may enhance cancer development under certain circumstances. One important process of cellular aging is oncogene-induced senescence, which acts as a significant anti-cancer mechanism. Cellular senescence resulting from damage caused by activated oncogenes prevents the growth of potentially neoplastic cells. Moreover, cells that have entered senescence appear to be targets for elimination by the innate immune system. In another aspect of cellular aging, the absence of telomerase activity in normal tissues results in such cells lacking a telomere maintenance mechanism. One consequence is that in aging there is an increase in cells with shortened telomeres. In the presence of active oncogenes that cause expansion of a neoplastic clone, shortening of telomeres, leading to telomere dysfunction, prevents the indefinite expansion of the clone, because the cells enter crisis. Crisis results from chromosome fusions and other defects caused by dysfunctional telomeres and is a terminal state of the neoplastic clone. In this way the absence of telomerase in human cells, while one cause of cellular aging, also acts as an anti-cancer mechanism.
衰老是随着时间的推移而表现出的各种变化，包括细胞水平的变化。细胞衰老主要作为一种肿瘤抑制机制，但在某些情况下也可能增强癌症的发展。细胞衰老的一个重要过程是致癌基因诱导的衰老，它作为一种重要的抗癌机制。由激活的致癌基因引起的损伤导致的细胞衰老阻止了潜在的肿瘤细胞的生长。此外，进入衰老状态的细胞似乎成为固有免疫系统消除的目标。在细胞衰老的另一个方面，正常组织中缺乏端粒酶活性导致这些细胞缺乏端粒维持机制。其结果是，随着年龄的增长，端粒缩短的细胞数量增加。在存在导致肿瘤克隆扩张的活跃致癌基因的情况下，端粒缩短导致端粒功能障碍，阻止了克隆的无限扩张，因为细胞进入危机。危机是由功能失调的端粒引起的染色体融合和其他缺陷引起的，是肿瘤克隆的终末状态。通过这种方式，人类细胞中端粒酶的缺失虽然是细胞衰老的一个原因，但也作为一种抗癌机制发挥作用。
