Anisimov Vladimir N
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, 68 Leningradskaya St., St. Petersburg 197758, Russia.
Crit Rev Oncol Hematol. 2003 Mar;45(3):277-304. doi: 10.1016/s1040-8428(02)00121-x.
The incidence of cancer increases with age in humans and in laboratory animals alike. There are different patterns of age-related distribution of tumors in different organs and tissues. Aging may increase or decrease the susceptibility of various tissues to initiation of carcinogenesis and usually facilitates promotion and progression of carcinogenesis. Aging may predispose to cancer by several mechanisms: (1) tissue accumulation of cells in late stages of carcinogenesis; (2) alterations in homeostasis, in particular, alterations in immune and endocrine system and (3) telomere instability linking aging and increased cancer risk. Increased susceptibility to the effects of tumor promoters is found both in aged animals and aged humans, as predicted by the multistage model of carcinogenesis. Available evidence supporting the relevance of replicative senescence of human cells and telomere biology to human cancer seems quite strong, however, the evidence linking cellular senescence to human aging is controversial and required additional studies. Data on the acceleration of aging by carcinogenic agents as well as on increased cancer risk in patients with premature aging are critically discussed. In genetically modified mouse models (transgenic, knockout or mutant) characterized by the aging delay, the incidence of tumors usually similar to those in controls, whereas the latent period of tumor development is increased. Practically all models of accelerated of aging in genetically modified animals show the increase in the incidence and the reduction in the latency of tumors. Strategies for cancer prevention must include not only measures to minimize exposure to exogenous carcinogenic agents, but also measures to normalize the age-related alterations in internal milieu. Life-span prolonging drugs (geroprotectors) may either postpone population aging and increase of tumor latency or decrease the mortality in long-living individuals in populations and inhibit carcinogenesis. At least some geroprotectors may increase the survival of a short-living individuals in populations but increase the incidence of malignancy.
在人类和实验动物中，癌症的发病率均会随着年龄的增长而升高。不同器官和组织中肿瘤的年龄相关分布模式各异。衰老可能会增加或降低各种组织对致癌作用起始阶段的易感性，并且通常会促进致癌作用的促进和进展。衰老可能通过多种机制引发癌症：（1）致癌作用晚期细胞在组织中的积累；（2）体内稳态的改变，尤其是免疫和内分泌系统的改变；（3）端粒不稳定将衰老与癌症风险增加联系起来。正如致癌作用多阶段模型所预测的那样，在老年动物和老年人中都发现了对肿瘤促进剂作用的易感性增加。现有证据支持人类细胞复制性衰老和端粒生物学与人类癌症的相关性，然而，将细胞衰老与人类衰老联系起来的证据存在争议，需要进一步研究。本文对致癌剂导致衰老加速的数据以及早衰患者患癌风险增加的数据进行了批判性讨论。在以衰老延迟为特征的基因改造小鼠模型（转基因、敲除或突变）中，肿瘤的发病率通常与对照组相似，而肿瘤发生的潜伏期会延长。实际上，基因改造动物中所有加速衰老的模型都显示肿瘤发病率增加且潜伏期缩短。癌症预防策略不仅必须包括尽量减少接触外源性致癌剂的措施，还必须包括使体内环境中与年龄相关的改变正常化的措施。延长寿命的药物（老年保护剂）可能会延缓人群衰老并延长肿瘤潜伏期，或者降低长寿人群中的死亡率并抑制致癌作用。至少一些老年保护剂可能会增加人群中短命个体的存活率，但会增加恶性肿瘤的发病率。
