Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock
Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock
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DOI：
10.1101/gad.1432206
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发表时间：
2006-07-15
影响因子：
10.5
通讯作者：
Antoch, Marina P.
中科院分区：
文献类型：
--
作者：
Kondratov, Roman V.;Kondratova, Anna A.;Antoch, Marina P.
缺乏昼夜节律转录因子BMAL 1（脑和肌肉ARNT样蛋白）的小鼠具有受损的昼夜节律行为，并表现出靶基因表达的节律性丧失。在这里，我们报告说，Bmal 1-/-小鼠寿命缩短，并显示出各种过早衰老的症状，包括肌肉减少症，白内障，皮下脂肪减少，器官萎缩等。早期衰老表型与Bmal 1-/-动物某些组织中活性氧水平的增加相关。这些发现，连同数据的时钟/BMAL 1依赖性控制的压力反应，可能提供了一个机制的解释，早期发病的年龄相关的病理在BMAL 1的情况下。
Mice deficient in the circadian transcription factor BMAL1 (brain and muscle ARNT-like protein) have impaired circadian behavior and demonstrate loss of rhythmicity in the expression of target genes. Here we report that Bmal1-/- mice have reduced lifespans and display various symptoms of premature aging including sarcopenia, cataracts, less subcutaneous fat, organ shrinkage, and others. The early aging phenotype correlates with increased levels of reactive oxygen species in some tissues of the Bmal1-/- animals. These findings, together with data on CLOCK/BMAL1-dependent control of stress responses, may provide a mechanistic explanation for the early onset of age-related pathologies in the absence of BMAL1.