Cerella Claudia, Grandjenette Cindy, Dicato Mario, Diederich Marc
Department of Pharmacy, College of Pharmacy, Seoul National University, Building 20 Room 303, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Korea.
Curr Drug Targets. 2016;17(4):405-15. doi: 10.2174/1389450116666150202155915.
Cancer and aging are two similar processes representing the final outcome of timedependent accumulation of various irreversible dysfunctions, mainly caused by stress-induced DNA and cellular damages. Apoptosis and senescence are two types of cellular response to damages that are altered in both cancer and aging, albeit through different mechanisms. Carcinogenesis is associated with a progressive reduction in the ability of the cells to trigger apoptosis and senescence. In contrast, in aging tissues, there is an increased accumulation of senescent cells, and the nature of apoptosis deregulation varies depending on the tissue. Thus, the prevailing model suggests that apoptosis and cellular senescence function as two essential tumor-suppressor mechanisms, ensuring the health of the individual during early and reproductive stages of life, but become detrimental and promote aging later in life. The recent discovery that various anticancer agents, including canonical inducers of apoptosis, act also as inducers of cellular senescence indicates that pro-senescence strategies may have applications in cancer prevention therapy. Therefore, dissection of the mechanisms mediating the delicate balance between apoptosis and cellular senescence will be beneficial in the therapeutic exploitation of both processes in the development of future anticancer and anti-aging strategies, including minimizing the side effects of such strategies. Here, we provide an overview of the roles of apoptosis and cellular senescence in cancer and aging.
癌症和衰老属于两个相似的过程,代表了各种不可逆功能障碍随时间积累的最终结果,这些功能障碍主要由应激诱导的DNA和细胞损伤所致。凋亡和衰老属于细胞对损伤的两种反应类型,在癌症和衰老过程中均会发生改变,尽管其机制有所不同。癌症发生与细胞触发凋亡和衰老的能力逐渐下降有关。相反,在衰老组织中,衰老细胞的积累会增加,且凋亡失调的性质因组织而异。因此,主流模型表明,凋亡和细胞衰老起着两种重要的肿瘤抑制机制的作用,在生命的早期和生殖阶段确保个体的健康,但在生命后期会变得有害并促进衰老。最近的发现表明,包括凋亡的经典诱导剂在内的各种抗癌药物也可作为细胞衰老的诱导剂,这表明促衰老策略可能在癌症预防治疗中具有应用价值。因此,剖析介导凋亡和细胞衰老之间微妙平衡的机制,将有助于在未来抗癌和抗衰老策略的开发中对这两个过程进行治疗性利用,包括尽量减少此类策略的副作用。在此,我们概述了凋亡和细胞衰老在癌症和衰老中的作用。