The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver
The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver
复制标题
小鼠肝脏衰老改变了线粒体基因表达和氧化应激调节的日常节律
DOI：
10.3109/07420528.2015.1085388
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发表时间：
2015-10-21
影响因子：
2.8
通讯作者：
Li, Xiaodong
中科院分区：
文献类型：
--
作者：
Gong, Changxia;Li, Chengwei;Li, Xiaodong
生物钟调节许多细胞过程，特别是包括细胞周期、新陈代谢和衰老。线粒体在代谢中起着重要作用，是细胞中活性氧（ROS）产生的主要部位。生物钟通过驱动NAD+水平和Sirt3活性的日常变化来调节线粒体功能。除了这个中心路线，在本研究中，我们发现一些线粒体基因的表达在肝脏中也是有节律的，并且这些节律在幼鼠中被ClockΔ19突变破坏，这表明它们是由核心昼夜节律振荡器调节的。与此相关的是，我们还发现肝脏对氧化应激的调节是有节律的。由于线粒体和ROS在衰老过程中发挥着重要作用，而线粒体功能也会受到衰老的干扰，这些相关的观察结果提示了一个令人信服的假设，即昼夜节律振荡器通过调节线粒体中的ROS来影响衰老。随着年龄的增长，肝脏中一些线粒体基因的表达节律发生改变，线粒体氧化应激动态的时间调控被打乱。然而，时钟基因的表达不受影响。我们的研究结果表明，线粒体功能是由生物钟和其他年龄依赖机制共同调节的，衰老通过生物钟下游的机制破坏线粒体节律。
The circadian clock regulates many cellular processes, notably including the cell cycle, metabolism and aging. Mitochondria play essential roles in metabolism and are the major sites of reactive oxygen species (ROS) production in the cell. The clock regulates mitochondrial functions by driving daily changes in NAD+ levels and Sirt3 activity. In addition to this central route, in the present study, we find that the expression of some mitochondrial genes is also rhythmic in the liver, and that there rhythms are disrupted by the ClockΔ19 mutation in young mice, suggesting that they are regulated by the core circadian oscillator. Related to this observation, we also find that the regulation of oxidative stress is rhythmic in the liver. Since mitochondria and ROS play important roles in aging, and mitochondrial functions are also disturbed by aging, these related observations prompt the compelling hypothesis that circadian oscillators influence aging by regulating ROS in mitochondria. During aging, the expression rhythms of some mitochondrial genes were altered in the liver and the temporal regulation over the dynamics of mitochondrial oxidative stress was disrupted. However, the expression of clock genes was not affected. Our results suggested that mitochondrial functions are combinatorially regulated by the clock and other age-dependent mechanism(s), and that aging disrupts mitochondrial rhythms through mechanisms downstream of the clock.