Kondratov Roman V, Vykhovanets Olena, Kondratova Anna A, Antoch Marina P
Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.
Aging (Albany NY). 2009 Dec 30;1(12):979-87. doi: 10.18632/aging.100113.
Deficiency of the circadian clock protein BMAL1 leads to premature aging and increased levels of reactivate oxygen species in several tissues of mice. In order to investigate the role of oxidative stress in accelerated aging and development of age-related pathologies, we continuously administered the antioxidant N-acetyl-L-cysteine toBmal1-deficient mice through their entire lifespan by supplementing drinking water. We found that the life long treatment with antioxidant significantly increased average and maximal lifespan and reduced the rate of age-dependent weight loss and development of cataracts. At the same time, it had no effect on time of onset and severity of other age-related pathologies characteristic of Bmal1-/- mice, such as joint ossification, reduced hair regrowth and sarcopenia. We conclude that chronic oxidative stress affects longevity and contributes to the development of at least some age-associated pathology, although ROS-independent mechanisms may also play a role. Our bioinformatics analysis identified the presence of a conservative E box element in the promoter regions of several genes encoding major antioxidant enzymes. We speculate that BMAL1 controls antioxidant defense by regulating the expression of major antioxidant enzymes.
生物钟蛋白BMAL1的缺乏会导致小鼠多个组织过早衰老以及活性氧水平升高。为了研究氧化应激在加速衰老和年龄相关病理发展中的作用，我们通过在饮用水中添加抗氧化剂N-乙酰-L-半胱氨酸，在Bmal1基因缺陷小鼠的整个生命周期内持续给药。我们发现，抗氧化剂的终身治疗显著延长了平均寿命和最大寿命，并降低了年龄依赖性体重减轻和白内障的发生率。同时，它对Bmal1-/-小鼠其他与年龄相关的病理特征的发病时间和严重程度没有影响，如关节骨化、毛发再生减少和肌肉减少症。我们得出结论，慢性氧化应激影响寿命，并至少促成了一些与年龄相关的病理发展，尽管不依赖活性氧的机制可能也起作用。我们的生物信息学分析确定在几个编码主要抗氧化酶的基因的启动子区域存在保守的E盒元件。我们推测BMAL1通过调节主要抗氧化酶的表达来控制抗氧化防御。
