The circadian clock gene period extends healthspan in aging Drosophila melanogaster.
The circadian clock gene period extends healthspan in aging Drosophila melanogaster.
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DOI：
10.18632/aging.100103
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发表时间：
2009-11-19
期刊：
影响因子：
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通讯作者：
Giebultowicz JM
中科院分区：
文献类型：
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作者：
Krishnan N;Kretzschmar D;Rakshit K;Chow E;Giebultowicz JM
有 越来越多的证据表明，衰老受生物钟（昼夜节律）的影响 - 协调基因表达每日变化的内部机制， 生理功能和行为与外部昼夜周期。 最近的数据表明，哺乳动物生物钟的破坏 导致加速老化和增加与年龄相关的病理， 癌症;然而，日常节奏的丧失和衰老之间的联系并不 明白我们试图确定昼夜节律的紊乱 生物钟影响模式生物果蝇的寿命和健康寿命 黑腹菌我们研究了昼夜节律中无效突变的影响， 时钟基因周期（per 01）对苍蝇的健康跨度， 用短期氧化应激（24小时高氧）挑战衰老果蝇 并调查他们在死亡率危险、 氧化损伤和功能性衰老。24小时高氧暴露 在中年时期， 而不是控制苍蝇。这种自我平衡的挑战也导致了 在per 01中氧化损伤的显著更高的积累 与对照组相比，此外，老化每01 果蝇表现出加速的功能衰退，如攀爬能力降低 与年龄匹配的对照组相比，神经元变性增加。 总之，这些数据表明，受损的压力防御途径可能 加速了突变体的衰老。另外我们 显示在年老的野生型中per基因的表达下降 苍蝇，表明昼夜调节网络受损， 随年龄
There is increasing evidence that aging is affected by biological (circadian) clocks - the internal mechanisms that coordinate daily changes in gene expression, physiological functions and behavior with external day/night cycles. Recent data suggest that disruption of the mammalian circadian clock results in accelerated aging and increased age-related pathologies such as cancer; however, the links between loss of daily rhythms and aging are not understood. We sought to determine whether disruption of the circadian clock affects lifespan and healthspan in the model organism Drosophila melanogaster. We examined effects of a null mutation in the circadian clock gene period (per01) on the fly healthspan by challenging aging flies with short-term oxidative stress (24h hyperoxia) and investigating their response in terms of mortality hazard, levels of oxidative damage, and functional senescence. Exposure to 24h hyperoxia during middle age significantly shortened the life expectancy in per01 but not in control flies. This homeostatic challenge also led to significantly higher accumulation of oxidative damage in per01 flies compared to controls. In addition, aging per01 flies showed accelerated functional decline, such as lower climbing ability and increased neuronal degeneration compared to age-matched controls. Together, these data suggest that impaired stress defense pathways may contribute to accelerated aging in the per mutant. In addition, we show that the expression of per gene declines in old wild type flies, suggesting that the circadian regulatory network becomes impaired with age.