Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Curr Opin Oncol. 2013 Jan;25(1):93-8. doi: 10.1097/CCO.0b013e32835b6358.
Advances in the health system and medical sciences are continuously pushing the barrier of life-expectancy. As a consequence, humans are being increasingly afflicted by age-associated diseases, such as cancer. The challenge now lies in understanding the mechanisms underlying ageing in order to reduce the lifetime risk for cancer.
In long-lived mammals, telomere length and restriction of telomerase activity are important barriers preventing the uncontrolled cell division. Absence of telomerase dictates the continuous telomere erosion with each cell division, thus restraining the proliferation of incipient tumour cells. However, recent findings have revealed the unintended consequences of telomere control of cell division. Cells with short telomeres accumulate in older individuals increasing the risk of telomere depletion. Loss of telomere protection results in tetraploidization and genomic instability characteristic of epithelial cancers. Additionally, telomere shortening blocks cell proliferation and induces cell senescence. Senescent cells secrete proinflammatory factors and reactive oxygen species that increase the likelihood of cellular transformation and create the perfect soil for cancer development.
Telomere shortening thus provides an example of antagonist pleiotropy, in which a beneficial characteristic that acts during the reproductive years of an organism may, later in life, contain the seed to its demise.
医疗体系和医学科学的进步正在不断推动人类预期寿命的延长。因此，人类越来越多地受到与年龄相关的疾病的困扰，如癌症。现在的挑战在于理解衰老的机制，以降低终生患癌的风险。
在长寿哺乳动物中，端粒长度和端粒酶活性的限制是阻止不受控制的细胞分裂的重要障碍。端粒酶的缺失导致每个细胞分裂时端粒的持续侵蚀，从而限制了初期肿瘤细胞的增殖。然而，最近的发现揭示了端粒控制细胞分裂的意外后果。端粒较短的细胞在老年人中积累，增加了端粒耗竭的风险。端粒保护的丧失导致四倍体和上皮癌特有的基因组不稳定性。此外，端粒缩短会阻止细胞增殖并诱导细胞衰老。衰老细胞分泌促炎因子和活性氧，增加细胞转化的可能性，并为癌症发展创造了完美的土壤。
总之，端粒缩短提供了一个拮抗多效性的例子，即在生物体繁殖期发挥作用的有益特征，可能在其生命后期成为其消亡的根源。
