The extent and significance of telomere loss with age
The extent and significance of telomere loss with age
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DOI：
10.1196/annals.1297.044
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Kipling, D
中科院分区：
文献类型：
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作者：
Baird, DM;Kipling, D
通过对某些人类细胞类型的增殖寿命施加限制，端粒丢失和随后的复制性衰老的发生被认为是导致与年龄相关的疾病的原因。虽然有大量的体外数据来揭示端粒侵蚀触发衰老的机制，但技术限制阻碍了我们了解体内端粒侵蚀的全部程度。到目前为止，我们有证据表明与年龄相关的端粒损失;然而，缺乏现有技术的分辨率不允许我们确定端粒侵蚀是否足够广泛，以触发体内复制衰老。再加上相当大的个体间异质性，以及年轻人和老年人之间端粒长度的重叠，使得任何相关性都很弱，意义也不清楚。然而，最近的技术发展，包括定量端粒荧光，原位杂交（Q-FISH），和基于PCR的单端粒长度分析（STELA）的适应，增加了端粒长度分析的分辨率。这些技术有望提供所需的证据，以解决人类衰老过程中端粒丢失的全部程度和意义。在这里，我们回顾已发表的数据端粒侵蚀的动态与年龄在人体内。
By imposing a limit on the proliferative life span of some human cell types, telomere loss and the subsequent onset of replicative senescence have been proposed to contribute to age-related disease. Although there is a large body of in vitro data to reveal the mechanisms by which telomere erosion triggers senescence, technical limitations have hampered our ability to understand the full extent of telomere erosion in vivo. Thus far, we have evidence of age-related telomere loss; however, the lack of resolution of existing technologies does not allow us to determine if telomere erosion is extensive enough to trigger replicative senescence in vivo. This coupled with the considerable interindividual heterogeneity, and the overlap in telomere lengths between young and elder individuals, render any correlation weak and the significance unclear. However, recent technical developments, including adaptations of quantitative telomere fluorescence, in situ hybridization (Q-FISH), and the PCR-based single telomere length analysis (STELA), have increased the resolution of telomere length analysis. These technologies promise to provide the evidence required to address the full extent and significance of telomere loss in the human aging process. Here, we review published data on the dynamics of telomere erosion with age in the human body.