Accelerometer-measured physical activity and sedentary behaviour are associated with C-reactive protein in US adults who get insufficient sleep: A threshold and isotemporal substitution effect analysis.

This study aimed to investigate the association between physical activity, sedentary behaviour and chronic inflammation in short sleep adults. The study included 2,113 NHANES participants with self-reported insufficient sleep. C-reactive protein (CRP) was used as the inflammatory biomarker. Physical activity and sedentary behaviour were objectively measured by accelerometers. Weighted regression model, two - piecewise linear regression model, and restricted cubic splines were applied to evaluate associations mentioned above. An isotemporal substitution model was used to assess the modelled effects of replacing sedentary time (ST) with moderate-to-vigorous levels of physical activity (MVPA) or light physical activity (LPA). After adjusting for potential confounding factors, higher levels of ST and lower levels of LPA or MVPA were associated with higher CRP levels. Isotemporal substitution analysis indicated that replacing 30 minutes of ST with 30 minutes of MVPA was associated with a significant decrease in CRP levels. Saturation analysis suggested that the association between MVPA and CRP may plateau at over 20 minutes of MVPA per day. Findings of this study provides insight into the potential benefits of replacing ST with MVPA. This study also suggests that increasing MVPA beyond a certain point may not provide additional anti-inflammatory benefits in a short sleep population.

Effects of sleep deprivation on food-related Pavlovian-instrumental transfer: a randomized crossover experiment.

Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals-sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating.

Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes.

Sleep disorders increase the risk and mortality of heart disease, but the brain-heart interaction has not yet been fully elucidated. Cuproptosis is a copper-dependent type of cell death activated by the excessive accumulation of intracellular copper. Here, we showed that 16 weeks of sleep fragmentation (SF) resulted in elevated copper levels in the male mouse heart and exacerbated myocardial ischemia-reperfusion injury with increased myocardial cuproptosis and apoptosis. Mechanistically, we found that SF promotes sympathetic overactivity, increases the germination of myocardial sympathetic nerve terminals, and increases the level of norepinephrine in cardiac tissue, thereby inhibits VPS35 expression and leads to impaired ATP7A related copper transport and copper overload in cardiomyocytes. Copper overload further leads to exacerbated cuproptosis and apoptosis, and these effects can be rescued by excision of the sympathetic nerve or administration of copper chelating agent. Our study elucidates one of the molecular mechanisms by which sleep disorders aggravate myocardial injury and suggests possible targets for intervention.

Melatonin improves maternal sleep deprivation-induced learning and memory impairment, inflammation, and synaptic dysfunction in murine male adult offspring.

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.

How BDNF affects working memory in acute sleep deprivation: The mediating role of spontaneous brain activity.

The brain-derived neurotrophic factor (BDNF) mediates the plasticity associated with memory processing, and compensatorily increases after acute sleep deprivation (SD). However, whether the altered spontaneous brain activity mediates the association between BDNF and working memory in SD remains unknown. Here, we aimed to probe the mediating role of the spontaneous brain activity between plasma BDNF and WM function in SD. A total of 30 healthy subjects with regular sleep were enrolled in this study. Resting-sate functional magnetic resonance imaging (fMRI) scans and the peripheral blood were collected before and after 24 h SD. All participants also received n-back task assessing working memory (WM) performance. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were calculated to reflect the intensity of regional spontaneous brain activity. Plasma BDNF was measured by sandwich ELISA. Our results revealed a significant decline in WM and increase in plasma BDNF level after SD, and negative association between the changed WM performance and plasma BDNF level. Specially, the ALFF of the left inferior parietal cortex and right inferior frontal cortex, and fALFF of the left anterior cingulate and medial prefrontal cortex and left posterior opercular cortex regulated the association between the BDNF and one-back reaction time respectively. Our results suggest that the association between BDNF and working memory may be mediated through regional spontaneous brain activity involving in the cerebral cortex, which may provide new sight into the interaction between neurotrophic factors and cognition, and potential targets for noninvasive brain stimulation on WM decline after acute SD.

Extracting Stress-Related EEG Patterns From Pre-Sleep EEG for Forecasting Slow-Wave Sleep Deficiency.

Sleep is vital to our daily activity. Lack of proper sleep can impair functionality and overall health. While stress is known for its detrimental impact on sleep quality, the precise effect of pre-sleep stress on subsequent sleep structure remains unknown. This study introduced a novel approach to study the pre-sleep stress effect on sleep structure, specifically slow-wave sleep (SWS) deficiency. To achieve this, we selected forehead resting EEG immediately before and upon sleep onset to extract stress-related neurological markers through power spectra and entropy analysis. These markers include beta/delta correlation, alpha asymmetry, fuzzy entropy (FuzzEn) and spectral entropy (SpEn). Fifteen subjects were included in this study. Our results showed that subjects lacking SWS often exhibited signs of stress in EEG, such as an increased beta/delta correlation, higher alpha asymmetry, and increased FuzzEn in frontal EEG. Conversely, individuals with ample SWS displayed a weak beta/delta correlation and reduced FuzzEn. Finally, we employed several supervised learning models and found that the selected neurological markers can predict subsequent SWS deficiency. Our investigation demonstrated that the classifiers could effectively predict varying levels of slow-wave sleep (SWS) from pre-sleep EEG segments, achieving a mean balanced accuracy surpassing 0.75. The SMOTE-Tomek resampling method could improve the performance to 0.77. This study suggests that stress-related neurological markers derived from pre-sleep EEG can effectively predict SWS deficiency. Such information can be integrated with existing sleep-improving techniques to provide a personalized sleep forecasting and improvement solution.

Total sleep deprivation effects on the attentional blink.

The Attentional Blink (AB) is a phenomenon that reflects difficulty in detecting or identifying the second of two successive targets (T1 and T2) that are presented in rapid succession, between 200-500ms apart. The AB involves indicators of attentional and temporal integration mechanisms related to the early stages of visual processing. The aim of this study was to identify the effects of 24-h of sleep deprivation (total sleep deprivation, TSD) on the attentional and temporal integration mechanisms of the AB. Twenty-two undergraduate students were recorded during five successive days, in these three conditions: baseline (two days), TSD (one day), and recovery (two days). Each day, at around 12:00 h, participants responded to a Rapid Serial Visual Presentation task (RSVP) that presented two targets separated by random intervals from 100 to 1000ms. The attentional mechanisms were assessed by the AB presence, the AB magnitude, and the AB interval, while the temporal integration mechanisms were evaluated by lag-1 sparing and order reversal responses. TSD negatively affected the attentional mechanisms, which is expressed by an overall reduction in performance, an extended AB interval, and a reduced AB magnitude. TSD also negatively affected the temporal integration mechanisms, manifested by an absence of lag-1 sparing and an increase in order reversals. These results suggest that people are still able to respond to two successive stimuli after 24 h without sleep. However, it becomes more difficult to respond to both stimuli because the attentional and temporal integration mechanisms of the AB are impaired.

Effects of paradoxical sleep deprivation on oxidative parameters in the serum and brain of mice submitted to the animal model of hyperglycemia.

The present study aimed to investigate the effects of paradoxical sleep deprivation (PSD) on behavioral and oxidative stress parameters in the brain and serum of mice submitted to the animal model of hyperglycemia induced by alloxan, mimicking the main symptom of diabetes mellitus (DM). Adults C57BL/6 male and female mice received an injection of alloxan, and ten days later, the animals were submitted to the PSD for 36 h. The animals' behavioral parameters were evaluated in the open-field test. Oxidative stress parameters [Diacetyldichlorofluorescein (DCF), Thiobarbituric acid reactive substances (TBARS), Superoxide dismutase (SOD), and Glutathione] were assessed in the frontal cortex, hippocampus, striatum, and serum. The PSD increased the male and female mice locomotion, but the alloxan's pre-administration prevented the PSD-induced hyperactivity. In addition, the male mice receiving alloxan and submitted to the PSD had elevated latency time in the first quadrant and the number of fecal boli, demonstrating increased anxiety-like behavior. The HPA-axis was hyperactivating in male and female mice pre-administered alloxan and/or PSD-submitted animals. The oxidative stress parameters were also increased in the serum of the animals administered alloxan and/or sleep-deprived mice. Despite alloxan or PSD leading to behavioral or biochemical alterations, the one did not potentiate the other in mice. However, more studies are necessary to identify the link between sleep and hyperglycemia.

Chronic sleep deprivation impairs retinal circadian transcriptome and visual function.

Sleep loss is common in modern society and is increasingly associated with eye diseases. However, the precise effects of sleep loss on retinal structure and function, particularly on the retinal circadian system, remain largely unexplored. This study investigates these effects using a chronic sleep deprivation (CSD) model in mice. Our investigation reveals that CSD significantly alters the retinal circadian transcriptome, leading to remarkable changes in the temporal patterns of enriched pathways. This perturbation extends to metabolic and immune-related transcriptomes, coupled with an accumulation of reactive oxygen species in the retina. Notably, CSD rhythmically affects the thickness of the ganglion cell complex, along with diurnal shifts in microglial migration and morphology within the retina. Most critically, we observe a marked decrease in both scotopic and photopic retinal function under CSD conditions. These findings underscore the broad impact of sleep deprivation on retinal health, highlighting its role in altering circadian gene expression, metabolism, immune response, and structural integrity. Our study provides new insights into the broader impact of sleep loss on retinal health.

Preoperative recovery sleep ameliorates postoperative cognitive dysfunction aggravated by sleep fragmentation in aged mice by enhancing EEG delta-wave activity and LFP theta oscillation in hippocampal CA1.

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

[Glymphatic dysfunction and sleep disorders: indirect effects on Alzheimer's disease]. / Glimfaticheskaya disfunktsiya i narusheniya sna: oposredovannoe vliyanie na bolezn' Al'tsgeimera.

Modern research raises the question of the potentially significant role of glymphatic dysfunction in the development of neurodegeneration and pathological aging. The exact molecular mechanisms are not yet fully understood, but there is ample evidence of a link between sleep deprivation and decreased clearance of ß-amyloid and other neurotoxin proteins that are associated with the development of neurodegenerative diseases, particularly Alzheimer's disease. The review analyzes current scientific information in this area of research, describes the latest scientific discoveries of the features of the glymphatic system, and also illustrates studies of markers that presumably indicate a deterioration in the glymphatic system. The relationship between sleep deprivation and pathophysiological mechanisms associated with neurodegenerative diseases is considered, and potential targets that can be used to treat or delay the development of these disorders are noted.

A resting-state EEG dataset for sleep deprivation.

To investigate the impact of sleep deprivation (SD) on mood, alertness, and resting-state electroencephalogram (EEG), we present an eyes-open resting-state EEG dataset. The dataset comprises EEG recordings and cognitive data from 71 participants undergoing two testing sessions: one involving SD and the other normal sleep. In each session, participants engaged in eyes-open resting-state EEG. The Psychomotor Vigilance Task (PVT) was employed for alertness measurement. Emotional and sleepiness were measured using Positive and Negative Affect Scale (PANAS) and Stanford Sleepiness Scale (SSS). Additionally, to examine the influence of individual sleep quality and traits on SD, Pittsburgh Sleep Quality Index (PSQI) and Buss-Perry Aggression Questionnaire (BPAQ) were utilized. This dataset's sharing may contribute to open EEG measurements in the field of SD.

Sleep deprivation increases the regularity of isometric torque fluctuations.

The regularity of the fluctuations present in torque signals represent the adaptability of the motor control. While previous research showed how it is affected by neuromuscular fatigue and ageing, the underlying mechanisms remain unclear. It is currently under debate whether these changes are explained by central or peripheral neuromuscular mechanisms. Here, we experimentally manipulated the sleep of thirteen young adults through a supervised 24 h-sleep deprivation protocol. This study aimed to investigate the effect of sleep deprivation on the regularity of torque fluctuations, and other standard torque-related outcomes (Peak Torque - PT - and Rate of Torque Development - RTD). The participants were asked to perform knee extension maximal voluntary contractions (MVC) and submaximal knee extensions at 40% of MVC for 30 s. PT and RTD were calculated from the MVC and the regularity of the torque fluctuations was determined on the submaximal task through Sample Entropy (SampEn). In addition, rate of perceived effort (RPE) was collected. We found no significant changes in PT and RTD. The regularity of torque fluctuations significantly increased (i.e., a decrease in SampEn) after 24 h-sleep deprivation (PRE = 1.76 ± 0.268, POS24 = 1.71 ± 0.306; p = 0.044). Importantly, we found a negative correlation between RPE and SampEn relative changes after sleep deprivation. This study brings new insights towards the understanding of the underlying mechanisms that explain changes in torque fluctuations, demonstrating that these changes are not limited to neuromuscular processes but are also likely to be affected by other domains, such as psychological profile, which can indirectly affect the neural drive to the muscles.

Baseline prepulse inhibition dependency of orexin A and REM sleep deprivation.

RATIONALE: Prepulse inhibition (PPI) impairment reflects sensorimotor gating problems, i.e. in schizophrenia. This study aims to enlighten the role of orexinergic regulation on PPI in a psychosis-like model. OBJECTIVES: In order to understand the impact of orexinergic innervation on PPI and how it is modulated by age and baseline PPI (bPPI), chronic orexin A (OXA) injections was carried on non-sleep-deprived and sleep-deprived rats that are grouped by their bPPI. METHODS: bPPI measurements were carried on male Wistar rats on P45 or P90 followed by grouping into low-PPI and high-PPI rats. The rats were injected with OXA twice per day for four consecutive days starting on P49 or P94, while the control groups received saline injections. 72 h REMSD was carried on via modified multiple platform technique on P94 and either OXA or saline was injected during REMSD. PPI tests were carried out 30 min. after the last injection. RESULTS: Our previous study with acute OXA injection after REMSD without bPPI grouping revealed that low OXA doses might improve REMSD-induced PPI impairment. Our current results present three important conclusions: (1) The effect of OXA on PPI is bPPI-dependent and age-dependent. (2) The effect of REMSD is bPPI-dependent. (3) The effect of OXA on PPI after REMSD also depends on bPPI. CONCLUSION: Orexinergic regulation of PPI response with and without REMSD can be predicted by bPPI levels. Our findings provide potential insights into the regulation of sensorimotor gating by sleep/wakefulness systems and present potential therapeutic targets for the disorders, where PPI is disturbed.

Effects of Acute Sleep Deprivation on the Physiological Response to Woodsmoke and Exercise.

OBJECTIVE: To evaluate sleep deprivation effects on the acute physiological response to a combined stressor of woodsmoke and exercise. METHODS: Ten participants completed two exercise trials (8 hours of sleep vs 4 hours) with woodsmoke. Trials were conducted in a crossover design. Key measures examined before and after each trial included heart rate variability, pulse wave velocity, blood pressure, pulmonary function testing, and oxidative stress. RESULTS: Acute sleep deprivation experienced before exercise and woodsmoke exposure did not impact metrics of heart rate variability, pulse wave velocity, pulmonary function testing, blood pressure, or oxidative stress. CONCLUSIONS: Acute sleep deprivation did not amplify physiologic metrics in response to moderate-intensity aerobic exercise with inhaled woodsmoke. Although findings do not eliminate the negative impacts of inhaling woodsmoke, more research is needed to understand the acute effects of woodsmoke exposure on the cardiovascular system. 1.

Effects of sleep deprivation on language-related brain functional connectivity: differences by gender and age.

Sleep deprivation (SD) negatively affects many cognitive functions, such as language performance. However, what remains unclear is whether and how SD affects the language-related brain network based on gender and age differences. The current study of 86 healthy adults used resting-state functional magnetic resonance imaging (rs-fMRI) to measure language-related functional connectivity after full sleep or partial SD. Gender and age differences in functional connectivity were assessed across four linguistic aspects: phonetics, morphology, semantics, and syntax. The results showed that SD can affect the connectivity status of language-related brain networks, especially syntax-related networks. Furthermore, the influence of SD on the functional connectivity in language-related networks differed between male and female groups, and between younger and older groups. Specifically, there were gender differences in the temporal association cortex and age differences in the parietal association cortex, during full sleep versus partial SD. These findings highlight changes in the brain's functional connectivity in response to SD as a potential source of gender and age differences in brain function.

Sleep loss and emotion: A systematic review and meta-analysis of over 50 years of experimental research.

In a largely sleep-deprived society, quantifying the effects of sleep loss on emotion is critical for promoting psychological health. This preregistered systematic review and meta-analysis quantified the effects of various forms of sleep loss on multiple aspects of emotional experiences. Eligible studies used experimental reductions of sleep via total sleep deprivation, partial sleep restriction, or sleep fragmentation in healthy populations to examine effects on positive affect, negative affect, general mood disturbances, emotional reactivity, anxiety symptoms, and/or depressive symptoms. In total, 1,338 effect sizes across 154 studies were included (N = 5,717; participant age range = 7-79 years). Random effects models were conducted, and all forms of sleep loss resulted in reduced positive affect (standardized mean difference [SMD] = -0.27 to -1.14), increased anxiety symptoms (SMD = 0.57-0.63), and blunted arousal in response to emotional stimuli (SMD = -0.20 to -0.53). Findings for negative affect, reports of emotional valence in response to emotional stimuli, and depressive symptoms were mixed and depended on the type of sleep loss. Nonlinear effects for the amount of sleep loss as well as differences based on the stage of sleep restricted (i.e., rapid eye movement sleep or slow-wave sleep) were also detected. This study represents the most comprehensive quantitative synthesis of experimental sleep and emotion research to date and provides strong evidence that periods of extended wakefulness, shortened sleep duration, and/or nighttime awakenings adversely influence human emotional functioning. Findings provide an integrative foundation for future research on sleep and emotion and elucidate the precise ways that inadequate sleep may impact our daytime emotional lives. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Low mindfulness is related to poor sleep quality from middle adolescents to emerging adults: a process model involving resilience and emotional dysfunction.

OBJECTIVES: Transitions from middle adolescence into merging adulthood, a life stage between age 15-25, has a high prevalence of sleep problems. Mindfulness is a trait defined as being attentive to the present moment which positively relates to sleep quality. In this study, we aimed to investigate how resilience and emotional dysfunction may influence the relationship between trait mindfulness and sleep quality. METHODS: The Five Facet Mindfulness Questionnaire, Connor-Davidson Resilience Scale, Pittsburgh Sleep Quality Index and Depression Anxiety Stress Scales were used to measure the key variables through an online survey of 497 participants between middle adolescence and emerging adults (317 females, mean age 18.27 ± 0.76 years). A process model was built to investigate the mediating roles of resilience and emotional dysfunction in the impact of trait mindfulness on sleep quality, together with the relationships between their specific components. RESULTS: We found a positive association between mindfulness and sleep quality through resilience and through emotional dysfunction, and through the sequential pathway from resilience to emotional dysfunction. Of note, acting with awareness (mindfulness facet) showed significant indirect effects on sleep quality, mediated by resilience and emotional dysfunction. CONCLUSIONS: Our findings may unveil the underlying mechanisms of how low mindfulness induces poor sleep quality. The findings indicate that conceiving mindfulness as a multifaceted construct facilitates comprehension of its components, relationships with other variables, and underscores its potential clinical significance given its critical implications for mental health.

Childhood adversity is associated with heightened inflammation after sleep loss.

OBJECTIVES: To investigate whether childhood adversity exacerbates the relationship between sleep restriction and inflammation. METHODS: Participants (N = 46) were randomly assigned to an experimental sleep restriction group (n = 25) or a night of typical sleep (n = 21). Participants provided a dried blood spot sample the morning before and after the experimental night. RESULTS: A significant interaction emerged between childhood adversity and group assignment on C-reactive protein (CRP) after the experimental night (Beta = -0.02, SE = 0.01, P = .03, 95% CI: -0.05, -0.002). Sleep restriction resulted in an increase in CRP at high levels of childhood adversity (+1 SD; Effect = -0.57, SE = 0.15, P< .001; 95% CI: -0.87, -0.26) but not low levels of childhood adversity (Effect = -0.08, SE = 0.10, P = .40; 95% CI: -0.29, 0.12). CONCLUSION: Childhood adversity may amplify the effect of sleep loss on markers of inflammation.

Hyperexcitable arousal circuits drive sleep instability during aging.

Sleep quality declines with age; however, the underlying mechanisms remain elusive. We found that hyperexcitable hypocretin/orexin (Hcrt/OX) neurons drive sleep fragmentation during aging. In aged mice, Hcrt neurons exhibited more frequent neuronal activity epochs driving wake bouts, and optogenetic activation of Hcrt neurons elicited more prolonged wakefulness. Aged Hcrt neurons showed hyperexcitability with lower KCNQ2 expression and impaired M-current, mediated by KCNQ2/3 channels. Single-nucleus RNA-sequencing revealed adaptive changes to Hcrt neuron loss in the aging brain. Disruption of Kcnq2/3 genes in Hcrt neurons of young mice destabilized sleep, mimicking aging-associated sleep fragmentation, whereas the KCNQ-selective activator flupirtine hyperpolarized Hcrt neurons and rejuvenated sleep architecture in aged mice. Our findings demonstrate a mechanism underlying sleep instability during aging and a strategy to improve sleep continuity.