生物钟核心成分BMAL1基因敲除小鼠的早衰及与年龄相关的病理变化。
Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock.
作者信息
Kondratov Roman V, Kondratova Anna A, Gorbacheva Victoria Y, Vykhovanets Olena V, Antoch Marina P
机构信息
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
出版信息
Genes Dev. 2006 Jul 15;20(14):1868-73. doi: 10.1101/gad.1432206.
Abstract
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.
摘要
缺乏昼夜节律转录因子BMAL1（脑和肌肉芳香烃受体核转运蛋白样蛋白）的小鼠具有受损的昼夜节律行为，并在靶基因表达中表现出节律性丧失。我们在此报告，Bmal1基因敲除小鼠寿命缩短，并表现出各种早衰症状，包括肌肉减少症、白内障、皮下脂肪减少、器官萎缩等。早衰表型与Bmal1基因敲除动物某些组织中活性氧水平升高相关。这些发现，连同关于应激反应的CLOCK/BMAL1依赖性控制的数据，可能为在缺乏BMAL1的情况下与年龄相关疾病的早发提供一个机制性解释。
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本文引用的文献
1
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Cell Cycle. 2006 Apr;5(8):890-5. doi: 10.4161/cc.5.8.2684. Epub 2006 Apr 17.
2
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FASEB J. 2006 Mar;20(3):530-2. doi: 10.1096/fj.05-5321fje. Epub 2006 Jan 25.
3
Exploiting the rodent model for studies on the pharmacology of lifespan extension.
Aging Cell. 2006 Feb;5(1):9-15. doi: 10.1111/j.1474-9726.2006.00185.x.
4
Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process.
FASEB J. 2006 Apr;20(6):720-2. doi: 10.1096/fj.05-5432fje. Epub 2006 Jan 25.
5
The molecular clock mediates leptin-regulated bone formation.
Cell. 2005 Sep 9;122(5):803-15. doi: 10.1016/j.cell.2005.06.028.
6
Sarcopenia of aging and its metabolic impact.
Curr Top Dev Biol. 2005;68:123-48. doi: 10.1016/S0070-2153(05)68005-2.
7
Suppression of aging in mice by the hormone Klotho.
Science. 2005 Sep 16;309(5742):1829-33. doi: 10.1126/science.1112766. Epub 2005 Aug 25.
8
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9
Aging human circadian rhythms: conventional wisdom may not always be right.
J Biol Rhythms. 2005 Aug;20(4):366-74. doi: 10.1177/0748730405277378.
10
Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging.
Science. 2005 Jul 15;309(5733):481-4. doi: 10.1126/science.1112125.
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