Effects of aging on the molecular circadian oscillations in Drosophila.
Effects of aging on the molecular circadian oscillations in Drosophila.
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DOI：
10.3109/07420528.2011.635237
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发表时间：
2012-02
影响因子：
2.8
通讯作者：
Giebultowicz JM
中科院分区：
文献类型：
--
作者：
Rakshit K;Krishnan N;Guzik EM;Pyza E;Giebultowicz JM
生物钟通过产生分子、细胞和生理功能的每日输出节律来维持时间的动态平衡。在人类、啮齿动物和果蝇的衰老过程中，输出节律，如睡眠/清醒周期和荷尔蒙波动，往往会恶化。然而，目前尚不清楚这种衰退是由核心转录时钟的缺陷引起的，还是由时钟输出通路的减弱引起的，或者两者兼而有之。作者监测了果蝇行为和分子节律随年龄的变化。衰老与休息/活动模式的中断和昼夜运动活动节律的自由跑动期的延长有关。在幼龄、中年和老年果蝇的头部和身体中测量了核心时钟基因的表达。四个时钟基因，周期，永恒，PAR结构域蛋白1ε和Vrille的转录振荡在衰老果蝇的头部显著减少，但在身体中没有。结果表明，这些基因转录水平的降低不是由于其由时钟和周期基因编码的激活子表达不足所致。有趣的是，尽管老年果蝇的周期抑制蛋白水平降低，但时钟周期复合体的转录激活功能受到了损害。这些数据表明，衰老改变了果蝇核心转录时钟的特性，从而使时钟的正极和负极都减弱了。
Circadian clocks maintain temporal homeostasis by generating daily output rhythms in molecular, cellular, and physiological functions. Output rhythms, such as sleep/wake cycles and hormonal fluctuations, tend to deteriorate during aging in humans, rodents, and fruit flies. However, it is not clear whether this decay is caused by defects in the core transcriptional clock, or weakening of the clock-output pathways, or both. The authors monitored age-related changes in behavioral and molecular rhythms in Drosophila melanogaster. Aging was associated with disrupted rest/activity patterns and lengthening of the free-running period of the circadian locomotor activity rhythm. The expression of core clock genes was measured in heads and bodies of young, middle-aged, and old flies. Transcriptional oscillations of four clock genes, period, timeless, Par domain protein 1ε, and vrille, were significantly reduced in heads, but not in bodies, of aging flies. It was determined that reduced transcription of these genes was not caused by the deficient expression of their activators, encoded by Clock and cycle genes. Interestingly, transcriptional activation by CLOCK-CYCLE complexes was impaired despite reduced levels of the PERIOD repressor protein in old flies. These data suggest that aging alters the properties of the core transcriptional clock in flies such that both the positive and the negative limbs of the clock are attenuated.
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影响因子：
5.3
作者：
HARDIN, PE
通讯作者：
HARDIN, PE
影响因子：
4.3
作者：
Antoch, Marina P.;Gorbacheva, Victoria Y.;Nikitin, Alexander Yu
通讯作者：
Nikitin, Alexander Yu
影响因子：
3.5
作者：
Hardin, PE
通讯作者：
Hardin, PE
影响因子：
10.5
作者：
Kondratov, Roman V.;Kondratova, Anna A.;Antoch, Marina P.
通讯作者：
Antoch, Marina P.
影响因子：
64.8
作者：
Ko, HW;Jiang, J;Edery, I
通讯作者：
Edery, I