Deletion of Ku86 causes early onset of senescence in mice
Deletion of Ku86 causes early onset of senescence in mice
复制标题
DOI：
10.1073/pnas.96.19.10770
复制
发表时间：
1999-09-14
影响因子：
11.1
通讯作者：
Hasty, P
中科院分区：
文献类型：
--
作者：
Vogel, H;Lim, DS;Hasty, P
在抗原受体组装过程中或暴露于电离辐射后形成的 DNA 双链断裂可由对非同源末端连接重要的蛋白质修复，这些蛋白质包括 Ku86、Ku70、DNA-PKCS、Xrcc4 和 DNA 连接酶 IV。我在这里展示了与对照同窝小鼠相比，ku86 突变小鼠过早表现出衰老特征的年龄特异性变化。包括骨质减少、皮肤萎缩、肝细胞变性、肝细胞包涵体、肝增生灶和年龄特异性死亡率。癌症和可能的败血症（由反应性免疫反应表明）在一定程度上导致了这两个队列的年龄特异性死亡率，并且这两种情况在 ku86(-/-) 小鼠中发生得更早。这些数据表明 Ku86 依赖性染色体代谢对于确定小鼠衰老特征的年龄特异性变化的开始非常重要。
DNA double-strand breaks formed during the assembly of antigen receptors or after exposure to ionizing radiation are repaired by proteins important for nonhomologous end joining that include Ku86, Ku70, DNA-PKCS, Xrcc4, and DNA ligase IV. Here me show that ku86-mutant mice, compared with control littermates, prematurely exhibited age-specific changes characteristic of senescence that. include osteopenia, atrophic skin, hepatocellular degeneration, hepatocellular inclusions, hepatic hyperplastic foci, and age-specific mortality. Cancer and likely sepsis (indicated by reactive immune responses) partly contributed to age-specific mortality for both cohorts, and both conditions occurred earlier in ku86(-/-) mice. These data indicate that Ku86-dependent chromosomal metabolism is important for determining the onset of age-specific changes characteristic of senescence in mice.