Aging differentially affects the re-entrainment response of central and peripheral circadian oscillators.
Aging differentially affects the re-entrainment response of central and peripheral circadian oscillators.
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DOI：
10.1523/jneurosci.3559-12.2012
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发表时间：
2012-11-14
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影响因子：
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通讯作者：
Davidson AJ
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文献类型：
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作者：
Sellix MT;Evans JA;Leise TL;Castanon-Cervantes O;Hill DD;DeLisser P;Block GD;Menaker M;Davidson AJ
衰老导致24小时行为、内分泌和代谢节律的幅度和精度下降，这些节律在哺乳动物中由视交叉上核（SCN）内的中央昼夜节律起搏器和外周组织中的局部振荡器调节。昼夜节律系统的破坏，如在跨子午线旅行期间所经历的，可能导致不利的健康后果，特别是在老年人中。为了检验对模拟时差反应的年龄相关变化将反映昼夜节律功能改变的假设，我们检查了年轻和老年PER 2：：荧光素酶小鼠的中央和外周振荡器的再夹带。与以前的研究一样，老年小鼠的运动活动节律在转移后需要比年轻小鼠更多的时间来重新吸引。在组织水平上，年龄对基线夹带的影响是明显的，老年小鼠显示早期阶段的大多数外周振荡器研究和后期阶段的细胞内的大多数SCN亚区。在光：暗循环提前6小时后，与年轻小鼠相比，老年小鼠显示出外周组织的再夹带速率较慢，但SCN反应更大、更快。因此，老化改变了昼夜节律计时系统的方式，差异影响中央和外周昼夜节律钟的再夹带响应。这种结果模式表明，老化的一个主要后果是起搏器振幅的降低，这将减缓外周振荡器的再夹带，并降低SCN对外部扰动的抵抗力。
Aging produces a decline in the amplitude and precision of 24h behavioral, endocrine, and metabolic rhythms, which are regulated in mammals by a central circadian pacemaker within the suprachiasmatic nucleus (SCN) and local oscillators in peripheral tissues. Disruption of the circadian system, as experienced during transmeridian travel, can lead to adverse health consequences, particularly in the elderly. To test the hypothesis that age-related changes in the response to simulated jetlag will reflect altered circadian function, we examined re-entrainment of central and peripheral oscillators from young and old PER2::luciferase mice. As in previous studies, locomotor activity rhythms in older mice required more days to re-entrain following a shift than younger mice. At the tissue level, effects of age on baseline entrainment were evident, with older mice displaying earlier phases for the majority of peripheral oscillators studied and later phases for cells within most SCN subregions. Following a 6h advance of the light:dark cycle, old mice displayed slower rates of re-entrainment for peripheral tissues but a larger, more rapid SCN response compared to younger mice. Thus, aging alters the circadian timing system in a manner that differentially affects the re-entrainment responses of central and peripheral circadian clocks. This pattern of results suggests that a major consequence of aging is a decrease in pacemaker amplitude, which would slow re-entrainment of peripheral oscillators and reduce SCN resistance to external perturbation.