title: Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.
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.
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany; Institute of Healthy Ageing, and Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Metaxakis
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Luke S
authors.initials: LS
authors.lastname: Tain
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany; Institute of Healthy Ageing, and Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grönke
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hendrich
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hinze
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Birras
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany; Institute of Healthy Ageing, and Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
authors.forename: Linda
authors.initials: L
authors.lastname: Partridge
mesh_terms: D000375:Aging; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D007301:Insect Hormones / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D009655:Octopamine / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics; D011954:Receptors, Dopamine / Q000096:biosynthesis; D018027:Receptors, Glucagon / Q000235:genetics; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism*; D013002:Somatomedins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C533337:AKHR protein, Drosophila; C111892:DIAP2 protein, Drosophila; D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D051034:Inhibitor of Apoptosis Proteins; D007301:Insect Hormones; D007328:Insulin; D009842:Oligopeptides; D011954:Receptors, Dopamine; D018027:Receptors, Glucagon; D013002:Somatomedins; C044833:adipokinetic hormone; D009655:Octopamine; D011972:Receptor, Insulin; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448959:ribosomal protein S6 kinase, 70kD, polypeptide 2; D011761:Pyrrolidonecarboxylic Acid; D004298:Dopamine; D020123:Sirolimus