Telomeres progressively shorten with age, and it has been proposed that critically short and dysfunctional telomeres contribute to aging and aging-associated diseases in humans. For many years it was thought that telomere erosion was strictly a consequence of the "end replication problem," or the inability of replicative polymerases to completely duplicate linear DNA ends. It is becoming increasingly evident, however, that telomere shortening of cultured human cells is also caused because of other replication defects in telomeric repeats, those that cause fragile telomeres and other aberrant telomeric structures that can be detected on metaphase chromosomes. Whether these replication defects contribute to telomere erosion also in human tissues is currently unknown. By analyzing peripheral blood mononuclear cells from a total of 35 healthy subjects ranging in age from 23 to 101 years, we demonstrated that telomeres increasingly display aberrant structures with advancing donor age. Although the percentages of fragile telomeres increased only until adulthood, the percentages of chromosomes displaying sister telomere loss and sister telomere chromatid fusions increased consistently throughout the entire human life span. Our data, therefore, suggest that telomeric replication defects other than the end replication problem contribute to aging-associated telomere erosion in humans.

中文翻译：

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端粒在衰老的人类中越来越发展出异常的结构。

端粒随着年龄的增长而逐渐缩短，并且已经提出严重短而功能失调的端粒会导致人类衰老和与衰老相关的疾病。多年以来，人们一直认为端粒侵蚀严格是“末端复制问题”或复制性聚合酶无法完全复制线性DNA末端的结果。然而，越来越明显的是，由于端粒重复序列中的其他复制缺陷，也导致了培养的人类细胞的端粒缩短，这些缺陷会导致易碎的端粒和其他异常的端粒结构，可以在中期染色体上检测到。目前尚不清楚这些复制缺陷是否也导致端粒侵蚀在人体组织中。通过分析来自35位年龄在23至101岁之间的健康受试者的外周血单核细胞，我们证明端粒随着供体年龄的增加而越来越显示出异常的结构。尽管脆弱的端粒的百分比仅在成年之前增加，但显示姐妹端粒丢失和染色体端粒染色单体融合的染色体百分比在整个人类寿命中一直持续增加。因此，我们的数据表明，除末端复制问题外，端粒复制缺陷还导致人类衰老相关的端粒侵蚀。在整个人类寿命中，显示姊妹端粒丢失和姊妹端粒染色单体融合的染色体百分比持续增加。因此，我们的数据表明，除末端复制问题外，端粒复制缺陷还导致人类衰老相关的端粒侵蚀。在整个人类寿命中，显示姊妹端粒丢失和姊妹端粒染色单体融合的染色体百分比持续增加。因此，我们的数据表明，除末端复制问题外，端粒复制缺陷还导致人类衰老相关的端粒侵蚀。