A bidirectional relationship between sleep and oxidative stress in Drosophila

Although sleep appears to be broadly conserved in animals, the physiological functions of sleep remain unclear. In this study, we sought to identify a physiological defect common to a diverse group of short-sleeping Drosophila mutants, which might provide insight into the function and regulation of sleep. We found that these short-sleeping mutants share a common phenotype of sensitivity to acute oxidative stress, exhibiting shorter survival times than controls. We further showed that increasing sleep in wild-type flies using genetic or pharmacological approaches increases survival after oxidative challenge. Moreover, reducing oxidative stress in the neurons of wild-type flies by overexpression of antioxidant genes reduces the amount of sleep. Together, these results support the hypothesis that a key function of sleep is to defend against oxidative stress and also point to a reciprocal role for reactive oxygen species (ROS) in neurons in the regulation of sleep.

• Publication year

  2018

• Venue

  PLoS Biology

• Publication date

  2018-07-01

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1371/journal.pbio.2005206PMID 30001323PMCID 6042693
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Selection for long and short sleep duration in Drosophila melanogaster reveals the complex genetic network underlying natural variation in sleep

  2017cited by this paper
• Reduced Sleep During Social Isolation Leads to Cellular Stress and Induction of the Unfolded Protein Response

  2017cited by this paper
• Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals.

  2017cited by this paper
• Neuronal substrates of sleep homeostasis; lessons from flies, rats and mice.

  2017cited by this paper
• translin Is Required for Metabolic Regulation of Sleep.

  2016cited by this paper
• Recurrent Sleep Fragmentation Induces Insulin and Neuroprotective Mechanisms in Middle-Aged Flies

  2016cited by this paper
• Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit.

  2016cited by this paper
• Unraveling the Evolutionary Determinants of Sleep.

  2016cited by this paper
• Amidated and Ibuprofen-Conjugated Kyotorphins Promote Neuronal Rescue and Memory Recovery in Cerebral Hypoperfusion Dementia Model

  2016cited by this paper
• Prevalence of Healthy Sleep Duration among Adults--United States, 2014.

  2016cited by this paper
• The two‐process model of sleep regulation: a reappraisal

  2016cited by this paper
• Behaviorally Assessed Sleep and Susceptibility to the Common Cold.

  2015cited by this paper
• Paradoxical sleep deprivation impairs mouse survival after infection with malaria parasites

  2015cited by this paper
• Diabetic Cardiovascular Disease Induced by Oxidative Stress

  2015cited by this paper
• Identification of Neurons with a Privileged Role in Sleep Homeostasis in Drosophila melanogaster.

  2015cited by this paper
• Sleep deficits but no metabolic deficits in premanifest Huntington's disease

  2015cited by this paper
• Sleep Facilitates Memory by Blocking Dopamine Neuron-Mediated Forgetting.

  2015cited by this paper
• Sleep restores behavioral plasticity to Drosophila mutants.

  2015cited by this paper
• Self-Rated Health in Healthy Adults and Susceptibility to the Common Cold

  2015cited by this paper
• SLEEPLESS is a bifunctional regulator of excitability and cholinergic synaptic transmission.

  2014cited by this paper
• ROS function in redox signaling and oxidative stress.

  2014cited by this paper
• Metabolic effects of sleep disruption, links to obesity and diabetes

  2014cited by this paper
• Increased sleep promotes survival during a bacterial infection in Drosophila.

  2014cited by this paper
• Ca(2+) mishandling and cardiac dysfunction in obesity and insulin resistance: role of oxidative stress.

  2014cited by this paper
• Altered regulation of sleep and feeding contributes to starvation resistance in Drosophila melanogaster

  2014cited by this paper
• Identification of Redeye, a new sleep-regulating protein whose expression is modulated by sleep amount

  2014cited by this paper
• Role of Vascular Oxidative Stress in Obesity and Metabolic Syndrome

  2014cited by this paper
• A New Wave

  2013cited by this paper
• Associations between change in sleep duration and inflammation: findings on C-reactive protein and interleukin 6 in the Whitehall II Study.

  2013cited by this paper
• Sleep Fragmentation and the Risk of Incident Alzheimer's Disease and Cognitive Decline in Older Persons.

  2013cited by this paper
• Chronic Sleep Fragmentation Promotes Obesity in Young Adult Mice

  2013cited by this paper
• Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series.

  2013cited by this paper
• ON OXIDATIVE STRESS AND DIABETIC COMPLICATIONS

  2013cited by this paper
• Sleep disturbance is associated with incident dementia and mortality.

  2013cited by this paper
• A GAL4-driver line resource for Drosophila neurobiology.

  2012cited by this paper
• Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery.

  2012cited by this paper
• Cul3 and the BTB Adaptor Insomniac Are Key Regulators of Sleep Homeostasis and a Dopamine Arousal Pathway in Drosophila

  2012cited by this paper
• Comparative pathology of bacteria in the genus Providencia to a natural host, Drosophila melanogaster.

  2011cited by this paper
• Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies.

  2011cited by this paper
• Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies.

  2011cited by this paper
• Inducing Sleep by Remote Control Facilitates Memory Consolidation in Drosophila

  2011cited by this paper
• insomniac and Cullin-3 regulate sleep and wakefulness in Drosophila.

  2011cited by this paper
• ROS signaling: the new wave?

  2011cited by this paper
• Oxidative stress and diabetic complications.

  2010cited by this paper
• Changes in components of energy regulation in mouse cortex with increases in wakefulness.

  2010cited by this paper
• Sleep duration and mortality: a systematic review and meta‐analysis

  2009cited by this paper
• pySolo: a complete suite for sleep analysis in Drosophila

  2009cited by this paper
• Heterozygous Mutation of Opa1 in Drosophila Shortens Lifespan Mediated through Increased Reactive Oxygen Species Production

  2009cited by this paper
• Hydrogen Peroxide Stimulates Activity and Alters Behavior in Drosophila melanogaster

  2009cited by this paper
• Complex I Is the Major Site of Mitochondrial Superoxide Production by Paraquat*

  2008cited by this paper
• Identification of SLEEPLESS, a Sleep-Promoting Factor

  2008cited by this paper
• Is Sleep Essential?

  2008cited by this paper
• Proteomic and oxidative stress analysis in human brain samples of Huntington disease.

  2008cited by this paper
• Effects of acute and chronic sleep loss on immune modulation of rats.

  2007cited by this paper
• Prolonged deprivation of sleep-like rest raises metabolic rate in the Pacific beetle cockroach, Diploptera punctata (Eschscholtz)

  2007cited by this paper
• Drosophila Hyperkinetic Mutants Have Reduced Sleep and Impaired Memory

  2007cited by this paper
• A role for the molecular chaperone protein BiP/GRP78 in Drosophila sleep homeostasis.

  2007cited by this paper
• Sleep and mortality: a population-based 22-year follow-up study.

  2007cited by this paper
• Waking Experience Affects Sleep Need in Drosophila

  2006cited by this paper
• Functional Dissection of a Neuronal Network Required for Cuticle Tanning and Wing Expansion in Drosophila

  2006cited by this paper
• Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation

  2006cited by this paper
• Sleep after learning aids memory recall.

  2006cited by this paper
• Sleep in Drosophila is regulated by adult mushroom bodies

  2006cited by this paper
• A Drosophila model for age-associated changes in sleep:wake cycles

  2006cited by this paper
• Brain oxidation is an initial process in sleep induction.

  2005cited by this paper
• Reduced sleep in Drosophila Shaker mutants

  2005cited by this paper
• Sleep deprivation induces the unfolded protein response in mouse cerebral cortex

  2005cited by this paper
• Dopamine Is a Regulator of Arousal in the Fruit Fly

  2005cited by this paper
• Theta activity in the waking EEG is a marker of sleep propensity in the rat.

  2005cited by this paper
• Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling.

  2005cited by this paper
• Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice.

  2004cited by this paper
• Sleep deprivation in honey bees 1

  2004cited by this paper
• Sleep deprivation and cellular responses to oxidative stress.

  2004cited by this paper
• Sleep homeostasis in Drosophila melanogaster.

  2004cited by this paper
• Role of oxidative stress in atherosclerosis.

  2003cited by this paper
• Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem

  2002cited by this paper
• Sleep deprivation in the rat: an update of the 1989 paper.

  2002cited by this paper
• Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death.

  2002cited by this paper
• Stress response genes protect against lethal effects of sleep deprivation in Drosophila

  2002cited by this paper
• Increases in amino-cupric-silver staining of the supraoptic nucleus after sleep deprivation.

  2002cited by this paper
• Sleep duration, illumination, and activity patterns in a population sample: effects of gender and ethnicity.

  2000cited by this paper
• Rest in Drosophila is a sleep-like state.

  2000cited by this paper
• Correlates of sleep and waking in Drosophila melanogaster.

  2000cited by this paper
• No evidence of brain cell degeneration after long-term sleep deprivation in rats.

  1999cited by this paper
• No evidence of brain cell degeneration after long-term sleep deprivation in rats.

  1999cited by this paper
• Sleep deprivation induces brain region‐specific decreases in glutathione levels

  1998cited by this paper
• Absence of oxidative stress following paradoxical sleep deprivation in rats.

  1997cited by this paper
• Partial night sleep deprivation reduces natural killer and celhdar immune responses in humans

  1996cited by this paper
• The free radical flux theory of sleep.

  1994cited by this paper
• Basal Lipid Peroxidation in Substantia Nigra Is Increased in Parkinson's Disease

  1989cited by this paper
• Animal sleep: a review of sleep duration across phylogeny.

  1984cited by this paper
• A two process model of sleep regulation.

  1982cited by this paper
• Author Contributions: ST, TY, and

  year unknowncited by this paper

• Fluctuations in Sleep Duration and Timing and Cardiometabolic Risk.

  2026cites this paper
• Early life sleep is associated with longevity in Drosophila

  2025influential citation
• Chrysanthemum morifolium extract protects HT22 cells from oxidative stress and enhances sleep via GABAergic modulation: contribution of luteolin‐7‐glucoside

  2025cites this paper
• Prevalence of sleep disorders among wood furniture workers occupationally exposed to dust and noise.

  2025cites this paper
• Physiological roles of reactive oxygen species in sleep homeostasis.

  2025cites this paper
• Presynaptic Release Probability Determines the Need for Sleep

  2025cites this paper
• Sleep Deprivation Primes Synaptic Vulnerability Without Inducing Oxidative Damage: A Mechanistic Reappraisal

  2025cites this paper
• Neurobiology of mitochondrial dynamics in sleep

  2025cites this paper
• Unhealthy lifestyles accelerated aging and consequential musculoskeletal morbidity

  2025cites this paper
• The role of sleep in multiple sclerosis.

  2025cites this paper
• Sex shapes the systemic response to light-induced sleep disruption in Drosophila melanogaster.

  2025cites this paper
• Data-driven approach to understand associations between dietary patterns, sleep problems, and mental health in adolescents.

  2025cites this paper
• Molecular Effects of Cornelian Cherry Fruit (Cornus mas L.) Extract on Sleep Deprivation-Induced Oxidative Stress, Cytokine Dysregulation, and Behavioural Changes in Wistar Rats

  2025cites this paper
• Healthy sleep without insomnia may go beyond sleep duration for achieving successful aging in Chinese older adults: a cross-sectional study

  2025cites this paper
• Rest, Repair, Repeat: The Complex Relationship of Autophagy and Sleep

  2025cites this paper
• Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevity

  2025cites this paper
• Hydrogen peroxide in midbrain sleep neurons regulates sleep homeostasis.

  2025cites this paper
• Integrative sleep management: from molecular pathways to conventional and herbal treatments

  2025cites this paper
• Sleep loss is a metabolic disorder.

  2025cites this paper
• Enhanced memory despite severe sleep loss in Drosophila insomniac mutants

  2025influential citation
• Ginsenoside Rc maintains sleep rhythm homeostasis by alleviating oxidative stress.

  2025cites this paper
• Distinct forms of amyloid-β moderate sleep duration through NAD+-linked redox metabolism in Alzheimer’s disease

  2025cites this paper
• Latitudinal Clines in Climate and Sleep Patterns Shape Disease Outcomes in Drosophila melanogaster Infected by Metarhizium anisopliae

  2025cites this paper
• Genome-wide identification and functional validation of the WW domain containing oxidoreductase gene associated with sleep duration

  2025cites this paper
• A carnitine transporter at the blood–brain barrier modulates sleep via glial lipid metabolism in Drosophila

  2025cites this paper
• Associations of phenols, parabens, and phthalates with biological aging: stratified analyses by chronological age and lifestyle in NHANES 2005–2010

  2025cites this paper
• A Lactobacillus consortium provides insights into the sleep-exercise-microbiome nexus in proof of concept studies of elite athletes and in the general population

  2025cites this paper
• Adaptive challenges of past and future invasion of Drosophila suzukii: insights from novel genomic resources and statistical methods combining individual and pool sequencing data

  2025cites this paper
• The Effect of Hyperbaric Oxygen in Reducing Blood Cortisol Levels in Patients with Sleep Disorders

  2024cites this paper
• Nicotine and Vape: Drugs of the Same Profile Flock Together

  2024cites this paper
• A male-killing Spiroplasma endosymbiont has age-mediated impacts on Drosophila endurance and sleep.

  2024cites this paper
• The association between oxidative balance score and sleep duration: a mediation analysis of a cross-sectional study

  2024cites this paper
• Differential regulation of sleep by blue, green, and red light in Drosophila melanogaster

  2024cites this paper
• Neuronal knockdown of Cullin3 as a Drosophila model of autism spectrum disorder

  2024cites this paper
• Continuous Theta Burst Stimulation Inhibits Oxidative Stress-Induced Inflammation and Autophagy in Hippocampal Neurons by Activating Glutathione Synthesis Pathway, Improving Cognitive Impairment in Sleep-Deprived Mice

  2024cites this paper
• The histone acylation reader ENL/AF9 regulates aging in Drosophila melanogaster.

  2024cites this paper
• Xiaoyin-anshen formula alleviates psoriasis complicated by sleep disturbances by regulating melatonin, antioxidant enzymes, and pro-inflammatory cytokines in mice

  2024cites this paper
• Environmental study and stress-related biomarkers modifications in a crew during analog astronaut mission EMMPOL 6

  2024cites this paper
• Association between dietary total antioxidant capacity and sleep problems and depressive symptoms among U.S. adults

  2024cites this paper
• Effect of Earthing Mats on Sleep Quality in Rats

  2024cites this paper
• Signals of energy availability in sleep: consequences of a fat-based metabolism

  2024cites this paper
• Cognitive hyperplasticity drives insomnia

  2024cites this paper
• Regulation of proteostasis by sleep through autophagy in Drosophila models of Alzheimer’s disease

  2024cites this paper
• Inflammation, oxidative stress and gut microbiome perturbation: A narrative review of mechanisms and treatment of the alcohol hangover.

  2024cites this paper
• Acute sleep deprivation (ASD) and cardioprotection: Impact of ASD on oxytocin-mediated sympathetic nervous activation preceding myocardial infarction.

  2024cites this paper
• Sleep and Oxidative Stress: Current Perspectives on the Role of NRF2

  2024cites this paper
• Characterization of GABA-loaded nanoliposomes and its health benefits

  2024cites this paper
• Altered Metabolism during the Dark Period in Drosophila Short Sleep Mutants.

  2024cites this paper
• Exploring the potential relationship between short sleep risks and cognitive function from the perspective of inflammatory biomarkers and cellular pathways: Insights from population‐based and mice studies

  2024cites this paper
• Elevated sleep quota in a stress-resilient Drosophila species.

  2024cites this paper
• Association between circulating antioxidants and sleep disorders: comprehensive results from NHANES 2017-2018.

  2024cites this paper
• Does glial lipid dysregulation alter sleep in Alzheimer's and Parkinson's disease?

  2024cites this paper
• Serum levels of neurotensin, pannexin-1, and sestrin-2 and the correlations with sleep quality or/and cognitive function in the patients with chronic insomnia disorder

  2024cites this paper
• Circadian rhythm regulates the function of immune cells and participates in the development of tumors

  2024cites this paper
• What happens when the lights are left on? Transcriptomic and phenotypic habituation to light pollution

  2024cites this paper
• Ghosts of parasites past influence current non-consumptive effects in Drosophila nigrospiracula.

  2024cites this paper
• The mechanisms of mitochondrial abnormalities that contribute to sleep disorders and related neurodegenerative diseases.

  2024cites this paper
• Insomnia in Forensic Detainees: Is Salience Network the Common Pathway for Sleep, Neuropsychiatric, and Neurodegenerative Disorders?

  2024cites this paper
• Sleep pressure accumulates in a voltage-gated lipid peroxidation memory

  2024cites this paper
• Predicting the impact of CPAP on brain health: A study using the sleep EEG‐derived brain age index

  2024cites this paper
• Association of Oxidative Stress and Proinflammation with Insomnia in Perimenopause

  2024cites this paper
• A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis

  2024cites this paper
• Drosophila melanogaster Sting mediates Coxiella burnetii infection by reducing accumulation of reactive oxygen species

  2024cites this paper
• Phylogenetic conservation of the interdependent homeostatic relationship of sleep regulation and redox metabolism

  2024cites this paper
• Sleep fragmentation induces heart failure in a hypertrophic cardiomyopathy mouse model by altering redox metabolism

  2024cites this paper
• Breaking free from the clock’s tyranny restores memory to brain damaged flies

  2024cites this paper
• Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus.

  2023cites this paper
• Increased interaction between endoplasmic reticulum and mitochondria following sleep deprivation

  2023cites this paper
• Activation of the Cap'n'collar C pathway (Nrf2 pathway in vertebrates) signaling in insulin pathway compromised Drosophila melanogaster flies ameliorates the diabetic state upon pro-oxidant conditions.

  2023cites this paper
• Chronic sleep loss sensitizes Drosophila melanogaster to nitrogen stress.

  2023cites this paper
• Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day

  2023cites this paper
• The Role of Natural Antioxidant Products That Optimize Redox Status in the Prevention and Management of Type 2 Diabetes

  2023cites this paper
• Wildfire-related smoke inhalation worsens cardiovascular risk in sleep disrupted rats

  2023cites this paper
• Elevated sleep need in a stress-resilient Drosophila species

  2023cites this paper
• Mitochondrial control of sleep.

  2023cites this paper
• Comparisons of lifespan and stress resistance between sexes in Drosophila melanogaster

  2023cites this paper
• Sleep Deprivation-Induced Oxidative Stress in Rat Models: A Scoping Systematic Review

  2023cites this paper
• A novel immune modulator IM33 mediates a glia-gut-neuronal axis that controls lifespan.

  2023cites this paper
• Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis

  2023cites this paper
• The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity

  2023cites this paper
• Prognostic Factors Associated With Sleep Duration: Serum Pro-Oxidant/Antioxidant Balance and Superoxide Dismutase 1 as Oxidative Stress Markers and Anxiety/Depression

  2023cites this paper
• Mild sleep restriction increases endothelial oxidative stress in female persons

  2023influential citation
• Social isolation shortens lifespan through oxidative stress in ants

  2023cites this paper
• Assessment of the glutathione system and the biomolecules oxidation products contribution to the state of free radical homeostasis in women of two ethnic groups with insomnia

  2023cites this paper
• Association of sleep quality and mitochondrial DNA copy number in healthy middle-aged adults.

  2023cites this paper
• Oxidative stress-mediated proapoptosis signaling: A novel theory on the mechanism underlying the pathogenesis of burning mouth syndrome.

  2023cites this paper
• Transcranial Irradiation Mitigates Paradoxical Sleep Deprivation Effect in an Age-Dependent Manner: Role of BDNF and GLP-1

  2023cites this paper
• Chronic dietary supplementation with nicotinamide riboside reduces sleep need in the laboratory mouse

  2023cites this paper
• The Effect of Hyperbaric Oxygen Therapy on Reducing Blood Cortisol Levels in Individuals with Anxiety Disorders

  2023cites this paper
• PROTECTIVE FEATURES OF LOBOPHORA VARIEGATA METHANOLIC EXTRACT (LVME) ON COGNITIVE BEHAVIOUR AND REDOX HOMEOSTASIS IN N-NITROSODIETHYLAMINE TREATED DROSOPHILA MELANOGASTER

  2022cites this paper
• New Perspectives on Sleep Regulation by Tea: Harmonizing Pathological Sleep and Energy Balance under Stress

  2022influential citation
• Role of Oxidative Stress and Inflammation in Insomnia Sleep Disorder and Cardiovascular Diseases: Herbal Antioxidants and Anti-inflammatory Coupled with Insomnia Detection Using Machine Learn-ing.

  2022cites this paper
• Self-reported sleep in relation to risk of dementia a quarter of a century later at age 90+: The 90+ Study

  2022cites this paper
• Sleep Disturbance, Irritability, and Response to Lurasidone Treatment in Children and Adolescents with Bipolar Depression

  2022cites this paper
• Association analyses of the autosomal genome and mitochondrial DNA with accelerometry-derived sleep parameters in depressed UK biobank subjects.

  2022cites this paper
• The Treatment of Parkinson's Disease with Sodium Oxybate.

  2022cites this paper
• Neurofibromin 1 mediates sleep depth in Drosophila

  2022cites this paper
• Ecdysone acts through cortex glia to regulate sleep in Drosophila

  2022cites this paper
• Glutamate, GABA and glutathione in adults with persistent post-concussive symptoms

  2022cites this paper
• Associations between oxidative stress markers and patient-reported smartphone-based symptoms in patients newly diagnosed with bipolar disorder: An exploratory study.

  2022cites this paper