文章：

癌症和衰老：互为对手的恶魔？

Cancer and ageing: rival demons?

原文发布日期：2003-05-01

DOI: 10.1038/nrc1073

类型: Review Article

开放获取: 否

要点：

1. Cancer is a problem that affects organisms with renewable tissues; these have evolved tumour-suppressor mechanisms to suppress the development of cancer.
2. Tumour-suppressor genes act to prevent or repair genomic damage (caretakers), or inhibit the propagation of potential cancer cells (gatekeepers) by permanently arresting their growth (cellular senescence) or inducing cell death (apoptosis).
3. Some caretaker tumour suppressors seem to postpone the development of ageing phenotypes, and so are also longevity-assurance genes.
4. The gatekeeper tumour-suppressor mechanisms (apoptosis and cellular senescence), by contrast, might promote certain ageing phenotypes.
5. Apoptosis and cellular senescence are controlled by the p53 and RB tumour-suppressor pathways, components of which are evolutionarily conserved among multicellular organisms.
6. The evolutionary hypothesis of antagonistic pleiotropy predicts that some processes that benefit young organisms (by suppressing cancer, for example) can have detrimental effects later in life and would therefore contribute to ageing.
7. Both apoptosis and cellular senescence might be antagonistically pleiotropic, promoting ageing by exhausting progenitor or stem cells. Additionally, senescent cells secrete factors that can disrupt tissue integrity and function, and even promote the progression of late-life cancers.
8. Recent studies on p53 provide a molecular basis for how tumour suppression and ageing might be intertwined.

要点翻译：

1. 癌症是影响具有可再生组织的生物体的问题；这些生物体已进化出肿瘤抑制机制来抑制癌症的发生。
2. 肿瘤抑制基因通过防止或修复基因组损伤（看守基因），或通过永久性终止细胞生长（细胞衰老）或诱导细胞死亡（凋亡）来抑制潜在癌细胞的增殖（看门基因）。
3. 部分看守型肿瘤抑制基因似乎能延缓衰老表型的出现，因此也被称为长寿保障基因。
4. 相比之下，看门型肿瘤抑制机制（凋亡和细胞衰老）则可能促进某些衰老表型。
5. 凋亡和细胞衰老受p53和RB肿瘤抑制通路调控，其组成元件在多细胞生物中具有进化保守性。
6. 拮抗性多效进化假说预测，某些对年轻生物体有益的过程（如抑制癌症）可能在生命后期产生有害效应，从而加速衰老。
7. 凋亡和细胞衰老可能均具有拮抗多效性——通过耗竭祖细胞或干细胞来促进衰老。此外，衰老细胞分泌的因子可能破坏组织完整性和功能，甚至促进晚年癌症的进展。
8. 近期关于p53的研究为肿瘤抑制与衰老之间的关联机制提供了分子基础。

英文摘要：

Organisms with renewable tissues use a network of genetic pathways and cellular responses to prevent cancer. The main mammalian tumour-suppressor pathways evolved from ancient mechanisms that, in simple post-mitotic organisms, act predominantly to regulate embryogenesis or to protect the germline. The shift from developmental and/or germline maintenance in simple organisms to somatic maintenance in complex organisms might have evolved at a cost. Recent evidence indicates that some mammalian tumour-suppressor mechanisms contribute to ageing. How might this have happened, and what are its implications for our ability to control cancer and ageing?

摘要翻译： 

具有可再生组织的生物体利用一套遗传通路和细胞反应网络来防止癌症。哺乳动物的主要肿瘤抑制通路起源于古老的机制，这些机制在简单的有丝分裂后生物中主要调控胚胎发育或保护生殖系。从简单生物中的发育和/或生殖系维持，转变为复杂生物中的体细胞维持，可能伴随着代价。最新证据表明，某些哺乳动物的肿瘤抑制机制会促进衰老。这是如何发生的？又对我们控制癌症和衰老的能力意味着什么？

原文链接：

Cancer and ageing: rival demons?