Age-related decline in circadian output.
Age-related decline in circadian output.
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DOI：
10.1523/jneurosci.0451-11.2011
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发表时间：
2011-07-13
期刊：
影响因子：
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通讯作者：
Block GD
中科院分区：
文献类型：
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作者：
Nakamura TJ;Nakamura W;Yamazaki S;Kudo T;Cutler T;Colwell CS;Block GD
睡眠/觉醒周期的中断，包括节律行为幅度的降低和睡眠片段的碎片化，通常与人类和其他哺乳动物的衰老有关。毫无疑问，造成这些变化的因素有很多，但大量文献表明，视交叉上核（SCN）中央生物钟与年龄相关的下降可能是造成这些变化的关键因素。为了探索 SCN 中与年龄相关的变化，我们对自由活动的年轻（3 – 5 个月）和中年（13 – 18 个月）小鼠的 SCN 进行了体内多单位神经活动（MUA）记录。重要的是，老年小鼠的 MUA 昼夜差异幅度显着降低。我们还发现室旁区（SPZ）的神经活动节律明显退化，室旁区是 SCN 的主要神经输出之一。令人惊讶的是，平行研究表明，通过 PER2 测量的 SCN 中的分子时钟机构在同一年龄仅表现出轻微的缺陷。因此，在视交叉上核神经活动节律水平上测量的昼夜节律输出会因衰老而降低，并且这种下降发生在分子钟表的关键组成部分被破坏之前。
Disruptions in sleep/wake cycles including decreased amplitude of rhythmic behaviors and fragmentation of the sleep episodes, are commonly associated with aging in humans and other mammals. While there are undoubtedly many factors contributing to these changes, a body of literature is emerging suggesting that an age-related decline in the central circadian clock in the suprachiasmatic nucleus (SCN) may be a key element responsible. To explore age-related changes in the SCN, we have carried out in vivo multiunit neural activity (MUA) recordings from the SCN of freely-moving young (3 – 5 mo) and middle-aged (13 – 18 mo) mice. Importantly, the amplitude of day-night difference in MUA was significantly reduced in the older mice. We also found that the neural activity rhythms are clearly degraded in the subparaventricular zone (SPZ), one of the main neural outputs of the SCN. Surprisingly, parallel studies indicate that the molecular clockwork in the SCN as measured by PER2 exhibited only minor deficits at this same age. Thus, the circadian output measured at the level of neural activity rhythms in the SCN is degraded by aging and this decline occurs before the disruption of key components of the molecular clockwork.