Sleep, aging, and lifespan in Drosophila.
Sleep, aging, and lifespan in Drosophila.
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DOI：
10.1186/1471-2202-11-56
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发表时间：
2010-04-29
期刊：
影响因子：
2.4
通讯作者：
Cirelli C
中科院分区：
文献类型：
--
作者：
Bushey D;Hughes KA;Tononi G;Cirelli C
对人类的流行病学研究表明，每天睡眠时间的减少与寿命的缩短有关，但这一问题仍然存在争议。对人类的其他研究也表明，睡眠数量和睡眠质量都会随着年龄的增长而减少。黑腹果蝇是研究衰老和睡眠的有用模型，遗传影响钾电流振荡器的突变会导致果蝇睡眠更少，寿命更短。然而，睡眠不足和寿命缩短之间的联系是否也存在于野生果蝇中尚不清楚。同样，目前尚不清楚这种联系是否取决于睡眠时间本身，而不是其他因素，如清醒时的活动。此外，老年果蝇的睡眠质量也有所下降，但尚不清楚与衰老相关的睡眠碎片是否是一种普遍现象。我们比较了3个携带高动力突变的短睡眠突变系(HK1、HKY和Hk2)和野生型兄弟姐妹的整个生命周期(所有果蝇都保持在20°C)。与野生型对照相比，HK1和HKY突变体在eClosure后第3天开始睡眠不足，而Hk2果蝇在大约两周后成为短睡者。与野生型果蝇相比，3个HK突变品系的寿命都有所缩短。总睡眠时间显示出随年龄增长的趋势，但这种影响在HK1和HKY果蝇中最为明显。在突变型和野生型品系中，睡眠质量都不会随着年龄的增长而下降，但对夜间睡眠的强烈偏好从“中年”开始下降。经Cox回归分析发现，HK1和HKY突变体及其对照品系的前2周和4周的总睡眠量与个体死亡风险呈负相关，而在HK2及其野生型对照品系中未发现相关关系。HK1和HKY突变体和它们的对照品系也显示出在头2周和4周内每天的总觉醒活动与危险之间的关联。然而，当睡眠时间和清醒活动同时用于回归时，活动的影响大大减弱，而大多数睡眠影响仍然显著。最后，HK1果蝇和野生型兄弟姐妹也在25°C下进行了测试，结果与20°C下的结果相似。即HK1突变体与对照组相比睡眠时间短、活动多、寿命短，两组的睡眠质量都不会随着年龄的增长而下降。不同的HK突变会影响睡眠表型，而且这种影响与年龄有关。在测试的6条线路中，有4条线路的睡眠与寿命变化显著相关，即使在消除任何活动影响后也是如此，但在睡眠影响消除后，活动与寿命没有显著关联。因此，除了环境因素和遗传背景外，睡眠也可能影响寿命。睡眠质量并不一定随着苍蝇年龄的增长而下降，这表明与衰老相关的睡眠碎片可能还取决于许多因素，包括遗传背景和饲养条件。
Epidemiological studies in humans suggest that a decrease in daily sleep duration is associated with reduced lifespan, but this issue remains controversial. Other studies in humans also show that both sleep quantity and sleep quality decrease with age. Drosophila melanogaster is a useful model to study aging and sleep, and inheriting mutations affecting the potassium current Shaker results in flies that sleep less and have a shorter lifespan. However, whether the link between short sleep and reduced longevity exists also in wild-type flies is unknown. Similarly, it is unknown whether such a link depends on sleep amount per se, rather than on other factors such as waking activity. Also, sleep quality has been shown to decrease in old flies, but it remains unclear whether aging-related sleep fragmentation is a generalized phenomenon. We compared 3 short sleeping mutant lines (Hk1, HkY and Hk2) carrying a mutation in Hyperkinetic, which codes for the beta subunit of the Shaker channel, to wild-type siblings throughout their entire lifespan (all flies kept at 20°C). Hk1 and HkY mutants were short sleeping relative to wild-type controls from day 3 after eclosure, and Hk2 flies became short sleepers about two weeks later. All 3 Hk mutant lines had reduced lifespan relative to wild-type flies. Total sleep time showed a trend to increase in all lines with age, but the effect was most pronounced in Hk1 and HkY flies. In both mutant and wild-type lines sleep quality did not decay with age, but the strong preference for sleep at night declined starting in "middle age". Using Cox regression analysis we found that in Hk1 and HkY mutants and their control lines there was a negative relationship between total sleep amount during the first 2 and 4 weeks of age and hazard (individual risk of death), while no association was found in Hk2 flies and their wild-type controls. Hk1 and HkY mutants and their control lines also showed an association between total daily wake activity over the first 2 and 4 weeks of age and hazard. However, when both sleep duration and wake activity were used in the same regression, the effects of activity were much reduced, while most of the sleep effects remained significant. Finally, Hk1 flies and wild-type siblings were also tested at 25°C, and results were similar to those at 20°C. Namely, Hk1 mutants were short sleeping, hyperactive, and short lived relative to controls, and sleep quality in both groups did not decrease with age. Different Hk mutations affect the sleep phenotype, and do so in an age-dependent manner. In 4 of the 6 lines tested sleep associates significantly with lifespan variation even after any effect of activity is removed, but activity does not associate significantly with lifespan after the effects of sleep are removed. Thus, in addition to environmental factors and genetic background, sleep may also affect longevity. Sleep quality does not necessarily decay as flies age, suggesting that aging-related sleep fragmentation may also depend on many factors, including genetic background and rearing conditions.
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影响因子：
2.8
作者：
Cajochen, C;Münch, M;Wirz-Justice, A
通讯作者：
Wirz-Justice, A
影响因子：
5.6
作者：
Ikehara, Satoyo;Iso, Hiroyasu;Temakoshi, Akiko
通讯作者：
Temakoshi, Akiko
影响因子：
3.3
作者：
Ekstedt, M;Åkerstedt, T;Söderström, M
通讯作者：
Söderström, M
影响因子：
5.6
作者：
Ferrie, Jane E.;Shipley, Martin J.;Marmot, Michael G.
通讯作者：
Marmot, Michael G.
DOI：
10.1523/jneurosci.4830-08.2009
发表时间：
2009-02-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bushey D;Tononi G;Cirelli C
通讯作者：
Cirelli C