von Figura Guido, Rudolph K Lenhard
Institut für Molekulare Medizin und Max-Planck-Forschungsgruppe für Stammzellalterung, Universität Ulm, Ulm, Deutschland.
Onkologie. 2009;32 Suppl 3:34-8. doi: 10.1159/000228653. Epub 2009 Sep 25.
Aging is the major risk factor for the development of cancer. An understanding of the molecular mechanisms that induce cancer formation during aging could help to develop cancer prevention strategies and improve cancer screening in the elderly. On the cellular level, it is of utmost importance to decipher molecular alterations leading to dysfunction and transformation of adult stem cells, since there is growing evidence that stem cells acquire the initial lesions that ultimately lead to cancer formation. On the molecular level, the accumulation of DNA damage and chromosomal instability represents a hallmark feature of cancer development in aged tissues. Different mechanisms can contribute to an accumulation of DNA damage and chromosomal instability during aging, including (i) telomere shortening, (ii) a reduction in DNA repair capacity, and (iii) the declining function of checkpoints (e. g. senescence, apoptosis). In addition, alterations in the cell environment can increase the selection of (pre-)malignant clones in aging tissues, involving (i) the loss of proliferative competition of non-transformed organ cells, (ii) the aberrant production of cytokines and growth factors, (iii) an impaired immune surveillance. In this review, we summarize experimental data on the functional role of these different mechanisms increasing the cancer risk during tissue aging.
衰老为癌症发生的主要风险因素。了解衰老过程中诱发癌症形成的分子机制有助于制定癌症预防策略并改善老年人的癌症筛查。在细胞水平上，破译导致成体干细胞功能障碍和转化的分子改变至关重要，因为越来越多的证据表明干细胞会获得最终导致癌症形成的初始损伤。在分子水平上，DNA损伤的积累和染色体不稳定性是衰老组织中癌症发展的标志性特征。衰老过程中，不同机制可导致DNA损伤积累和染色体不稳定性，包括：（i）端粒缩短；（ii）DNA修复能力降低；（iii）检查点功能衰退（如衰老、凋亡）。此外，细胞环境的改变会增加衰老组织中（前）恶性克隆的选择，涉及：（i）未转化的器官细胞增殖竞争丧失；（ii）细胞因子和生长因子异常产生；（iii）免疫监视受损。在本综述中，我们总结了关于这些不同机制在组织衰老过程中增加癌症风险的功能作用的实验数据。
