Aging impairs circadian clock function, leading to disrupted sleep-wake patterns and a reduced capability to adapt to changes in environmental light conditions. This makes shift work or the changing of time zones challenging for the elderly and, importantly, is associated with the development of age-related diseases. However, it is unclear what levels of the clock machinery are affected by aging, which is relevant for the development of targeted interventions. We found that naturally aged mice of >24 months had a reduced rhythm amplitude in behavior compared with young controls (3-6 months). Moreover, the old animals had a strongly reduced ability to adapt to short photoperiods. Recording PER2::LUC protein expression in the suprachiasmatic nucleus revealed no impairment of the rhythms in PER2 protein under the 3 different photoperiods tested (LD: 8:16, 12:12, and 16:8). Thus, we observed a discrepancy between the behavioral phenotype and the molecular clock, and we conclude that the aging-related deficits emerge downstream of the core molecular clock. Since it is known that aging affects several intracellular and membrane components of the central clock cells, it is likely that an impairment of the interaction between the molecular clock and these components is contributing to the deficits in photoperiod adaptation.

中文翻译：

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老化会影响中央分子钟下游的光周期适应能力。

衰老会损害昼夜节律功能，导致睡眠-觉醒模式中断，并降低适应环境光照条件的能力。这使老年人的轮班工作或时区的改变具有挑战性，并且重要的是，它与年龄相关疾病的发展有关。但是，尚不清楚时钟设备的哪个级别受老化影响，这与有针对性的干预措施的发展有关。我们发现，与年轻对照组（3-6个月）相比，年龄大于24个月的自然衰老小鼠的行为节律振幅降低。此外，这些老动物适应短光周期的能力大大降低。记录PER2 ：：在3种不同的光周期下（LD：8：16、12：12和16：8），视交叉上核中的LUC蛋白表达未显示PER2蛋白的节律受损。因此，我们观察到行为表型和分子钟之间的差异，并且我们得出结论，与衰老相关的缺陷出现在核心分子钟的下游。由于已知衰老会影响中央时钟细胞的一些细胞内和膜成分，因此分子时钟与这些成分之间相互作用的损害很可能导致光周期适应性缺陷。