Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.

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-...

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Main Authors: Athanasios Metaxakis, Luke S Tain, Sebastian Grönke, Oliver Hendrich, Yvonne Hinze, Ulrike Birras, Linda Partridge
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-04-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.1001824
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author Athanasios Metaxakis
Luke S Tain
Sebastian Grönke
Oliver Hendrich
Yvonne Hinze
Ulrike Birras
Linda Partridge
author_facet Athanasios Metaxakis
Luke S Tain
Sebastian Grönke
Oliver Hendrich
Yvonne Hinze
Ulrike Birras
Linda Partridge
author_sort Athanasios Metaxakis
collection DOAJ
description 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.
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institution Kabale University
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publisher Public Library of Science (PLoS)
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spelling doaj-art-7cd5b48fc88141e1bb9469141b4723e42025-08-20T03:46:12ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852014-04-01124e100182410.1371/journal.pbio.1001824Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.Athanasios MetaxakisLuke S TainSebastian GrönkeOliver HendrichYvonne HinzeUlrike BirrasLinda PartridgeSleep 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.https://doi.org/10.1371/journal.pbio.1001824
spellingShingle Athanasios Metaxakis
Luke S Tain
Sebastian Grönke
Oliver Hendrich
Yvonne Hinze
Ulrike Birras
Linda Partridge
Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.
PLoS Biology
title Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.
title_full Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.
title_fullStr Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.
title_full_unstemmed Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.
title_short Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.
title_sort lowered insulin signalling ameliorates age related sleep fragmentation in drosophila
url https://doi.org/10.1371/journal.pbio.1001824
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