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Lowered Insulin Signalling Ameliorates Age-Related Sleep Fragmentation in Drosophila

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Metaxakis,  Athanasios
Biological Mechanisms of Ageing, Department Partridge, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Tain,  Luke
Biological Mechanisms of Ageing, Department Partridge, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Grönke,  Sebastian
Biological Mechanisms of Ageing, Department Partridge, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Hendrich,  Oliver
Biological Mechanisms of Ageing, Department Partridge, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Hinze,  Yvonne
Bio-MS, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Birras,  Ulrike
Biological Mechanisms of Ageing, Department Partridge, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Partridge,  Linda
Biological Mechanisms of Ageing, Department Partridge, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Citation

Metaxakis, A., Tain, L., Grönke, S., Hendrich, O., Hinze, Y., Birras, U., et al. (2014). Lowered Insulin Signalling Ameliorates Age-Related Sleep Fragmentation in Drosophila. PLOS BIOLOGY, 12(4): e1001824. doi:10.1371/journal.pbio.1001824.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0019-D274-D
Abstract
Sleep fragmentation, particularly reduced and interrupted night sleep, impairs the quality of life of older people. Strikingly similar declines in sleep quality are seen during ageing in laboratory animals, including the fruit fly Drosophila. We investigated whether reduced activity of the nutrient- and stress-sensing insulin/insulin-like growth factor (IIS)/TOR signalling network, which ameliorates ageing in diverse organisms, could rescue the sleep fragmentation of ageing Drosophila. Lowered IIS/TOR network activity improved sleep quality, with increased night sleep and day activity and reduced sleep fragmentation. Reduced TOR activity, even when started for the first time late in life, improved sleep quality. The effects of reduced IIS/TOR network activity on day and night phenotypes were mediated through distinct mechanisms: Day activity was induced by adipokinetic hormone, dFOXO, and enhanced octopaminergic signalling. In contrast, night sleep duration and consolidation were dependent on reduced S6K and dopaminergic signalling. Our findings highlight the importance of different IIS/TOR components as potential therapeutic targets for pharmacological treatment of age-related sleep fragmentation in humans.