Deficiency of circadian protein CLOCK reduces lifespan and increases age-related cataract development in mice.
Deficiency of circadian protein CLOCK reduces lifespan and increases age-related cataract development in mice.
复制标题
DOI：
10.18632/aging.100241
复制
发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Kondratov RV
中科院分区：
文献类型：
--
作者：
Dubrovsky YV;Samsa WE;Kondratov RV
生物钟与衰老的调节有关。转录因子Clock是昼夜节律系统的核心组成部分，与另一种昼夜节律时钟蛋白BMAL1形成复合体。最近的研究表明，BMAL1缺乏会导致小鼠的早衰。在这里，我们研究了缺乏时钟蛋白的小鼠的衰老。Clock蛋白缺乏显著影响寿命：Clock−/−小鼠的平均寿命比野生型小鼠减少了15%，而最高寿命减少了20%以上。时钟缺乏还会导致这些小鼠患上两种特定年龄的疾病，即白内障和皮炎，其发生率远远高于野生型小鼠。与BMAL1缺乏的动物相比，Clock−/−小鼠不会出现过早衰老的表型，也不会出现BMAL1缺乏的多种与年龄相关的病理特征。因此，尽管Clock和BMAL1形成了转录复合体，但它们缺乏的生理结果是不同的。我们的结果表明，时钟在衰老中起着重要作用，特别是时钟活动对调节正常生理以及晶状体和皮肤的衰老至关重要。
Circadian clock is implicated in the regulation of aging. The transcription factor CLOCK, a core component of the circadian system, operates in complex with another circadian clock protein BMAL1. Recently it was demonstrated that BMAL1 deficiency results in premature aging in mice. Here we investigate the aging of mice deficient for CLOCK protein. Deficiency of the CLOCK protein significantly affects longevity: the average lifespan of Clock−/− mice is reduced by 15% compared with wild type mice, while maximum lifespan is reduced by more than 20%. CLOCK deficiency also results in the development of two age-specific pathologies in these mice, cataracts and dermatitis, at a much higher rate than in wild type mice. In contrast to BMAL1 deficient animals, Clock−/− mice do not develop a premature aging phenotype and do not develop the multiple age-associated pathologies characteristic of BMAL1 deficiency. Thus, although CLOCK and BMAL1 form a transcriptional complex, the physiological result of their deficiency is different. Our results suggest that CLOCK plays an important role in aging, specifically; CLOCK activity is critical for the regulation of normal physiology and aging of the lens and skin.
登录
查看更多内容
影响因子：
4.5
作者：
Lin KK;Kumar V;Geyfman M;Chudova D;Ihler AT;Smyth P;Paus R;Takahashi JS;Andersen B
通讯作者：
Andersen B
影响因子：
4.3
作者：
Antoch, Marina P.;Gorbacheva, Victoria Y.;Nikitin, Alexander Yu
通讯作者：
Nikitin, Alexander Yu
影响因子：
56.9
作者：
Reick, M;Garcia, JA;McKnight, SL
通讯作者：
McKnight, SL
影响因子：
10.5
作者：
Kondratov, Roman V.;Kondratova, Anna A.;Antoch, Marina P.
通讯作者：
Antoch, Marina P.
影响因子：
5.3
作者：
Bertolucci, Cristiano;Cavallari, Nicola;Pinotti, Mirko
通讯作者：
Pinotti, Mirko