Nelson David M, McBryan Tony, Jeyapalan Jessie C, Sedivy John M, Adams Peter D
Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Age (Dordr). 2014 Jun;36(3):9637. doi: 10.1007/s11357-014-9637-0. Epub 2014 Mar 20.
Cellular senescence is a stable proliferation arrest associated with an altered secretory pathway, the senescence-associated secretory phenotype. However, cellular senescence is initiated by diverse molecular triggers, such as activated oncogenes and shortened telomeres, and is associated with varied and complex physiological endpoints, such as tumor suppression and tissue aging. The extent to which distinct triggers activate divergent modes of senescence that might be associated with different physiological endpoints is largely unknown. To begin to address this, we performed gene expression profiling to compare the senescence programs associated with two different modes of senescence, oncogene-induced senescence (OIS) and replicative senescence (RS [in part caused by shortened telomeres]). While both OIS and RS are associated with many common changes in gene expression compared to control proliferating cells, they also exhibit substantial differences. These results are discussed in light of potential physiological consequences, tumor suppression and aging.
细胞衰老表现为一种稳定的增殖停滞，与分泌途径改变即衰老相关分泌表型有关。然而，细胞衰老由多种分子触发因素引发，如激活的癌基因和缩短的端粒，并与多种复杂的生理终点相关，如肿瘤抑制和组织衰老。不同的触发因素在多大程度上激活可能与不同生理终点相关的不同衰老模式，目前尚不清楚。为了开始解决这个问题，我们进行了基因表达谱分析，以比较与两种不同衰老模式相关的衰老程序，即癌基因诱导的衰老（OIS）和复制性衰老（RS[部分由端粒缩短引起]）。与对照增殖细胞相比，OIS和RS都与许多基因表达的常见变化相关，但它们也表现出显著差异。我们根据潜在的生理后果、肿瘤抑制和衰老对这些结果进行了讨论。
