Decreased expression of DNA repair proteins Ku70 and Mre11 is associated with aging and may contribute to the cellular senescence
Decreased expression of DNA repair proteins Ku70 and Mre11 is associated with aging and may contribute to the cellular senescence
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DOI：
10.1038/emm.2006.81
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发表时间：
2006-12-31
影响因子：
12.8
通讯作者：
Park, Gil-Hong
中科院分区：
文献类型：
--
作者：
Ju, Yeun-Jin;Lee, Kee-Ho;Park, Gil-Hong
端粒DNA的逐渐丢失会导致复制性衰老，因此，具有较长的端粒DNA通常被认为可以提供较长的寿命。端粒DNA的维持和稳定离不开多种DNA结合蛋白的结合，包括参与双链断裂（DSB）修复的蛋白。我们推断，老年人DSB修复能力的下降和端粒缩短的增加可能与能够结合端粒的DSB修复蛋白的表达减少有关。我们的数据显示，在测试的DSB修复蛋白中，只有Ku70和Mre11的表达在人淋巴细胞中表现出具有统计学意义的年龄依赖性变化。此外，我们发现Ku70和Mre11的表达具有统计学相关性，这表明Ku70和Mre11的功能可能相关。其余的DSB修复蛋白Sir2、TRF1和Ku80在衰老过程中均无显著差异。根据这些数据，生活在区域社区（长寿组）的人比其他地区的人平均寿命更长，其Ku70表达水平高于邻近对照社区的人。综上所述，我们的数据首次表明Ku70和Mre11可能是衰老的新生物标志物，并进一步表明维持Ku70和Mre11的高表达可能是长寿组延长寿命的原因。
The gradual loss of telomeric DNA can contribute to replicative senescence and thus, having longer telomeric DNA is generally considered to provide a longer lifespan. Maintenance and stabilization of telomeric DNA is assisted by binding of multiple DNA-binding proteins, including those involved in double strand break (DSB) repair. We reasoned that declining DSB repair capacity and increased telomere shortening in aged individuals may be associated with decreased expression of DSB repair proteins capable of telomere binding. Our data presented here show that among the DSB repair proteins tested, only the expression of Ku70 and Mre11 showed statistically significant age-dependent changes in human lymphocytes. Furthermore, we found that expressions of Ku70 and Mre11 are statistically correlated, which indicate that the function of Ku70 and Mre11 may be related. All the other DSB repair proteins tested, Sir2, TRF1 and Ku80, did not show any significant differences upon aging. In line with these data, people who live in the regional community (longevity group), which was found to have statistically longer average life span than the rest area, shows higher level of Ku70 expression than those living in the neighboring control community. Taken together, our data show, for the first time, that Ku70 and Mre11 may represent new biomarkers for aging and further suggest that maintenance of higher expression of Ku70 and Mre11 may be responsible for keeping longer life span observed in the longevity group.