Möller Peter, Mayer Susanne, Mattfeldt Torsten, Müller Kathrin, Wiegand Peter, Brüderlein Silke
Ulm University, Institute of Pathology, 89081 Ulm, Germany.
Aging (Albany NY). 2009 Jul 14;1(8):733-9. doi: 10.18632/aging.100068.
Telomeres are repetitive DNA sequences at chromosomal ends contributing to genomic integrity. In somatic cells, telomeres are shortened during DNA reduplication. Thus, telomere erosion has been regarded as a biological clock. Applying the telomere/centromere (T/C)-FISH technique to human peripheral blood lymphocytes, we showed that pangenomically, telomere shortening is linear in centenarians and that this attrition is delayed in females. Statistics reveal a greater skewness in telomere length distribution in females. As the morphological correlate, we find abnormally long telomeres distributed at random. This "erratic extensive elongation" (EEE) of telomeres is a hitherto unrecognized phenomenon in non-neoplastic cells, and females are more successful in this respect. As evidenced by endoreduplication, EEE is transmitted to the cells' progeny. The mechanism involved is likely to be the alternative pathway of telomere elongation (ALT), counteracting erosion and already known to operate in neoplastic cells.
端粒是染色体末端的重复DNA序列,有助于基因组完整性。在体细胞中,端粒在DNA复制过程中缩短。因此,端粒侵蚀被视为一种生物钟。将端粒/着丝粒(T/C)-FISH技术应用于人类外周血淋巴细胞,我们发现,从全基因组来看,百岁老人的端粒缩短呈线性,且女性的这种损耗延迟。统计数据显示女性端粒长度分布的偏度更大。作为形态学上的相关特征,我们发现异常长的端粒随机分布。端粒的这种“不稳定的广泛延长”(EEE)是迄今在非肿瘤细胞中未被认识到的现象,女性在这方面更为明显。经核内复制证明,EEE会传递给细胞后代。其涉及的机制可能是端粒延长的替代途径(ALT),它可抵消侵蚀,并且已知在肿瘤细胞中发挥作用。