Genetic Markers of Differential Vulnerability to Sleep Loss in Adults.
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ABSTRACT:
SUBMITTER: Casale CE
PROVIDER: S-EPMC8464868 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Short sleep duration is a risk factor for increased hunger and caloric intake, late-night eating, attenuated fat loss when dieting, and for weight gain and obesity. It is unknown whether altered energy-balance responses to sleep loss are stable (phenotypic) over time, and the extent to which individuals differ in vulnerability to such responses. Healthy adults experienced two laboratory exposures to sleep restriction separated by 60-2132 days. Caloric intake, meal timing and weight were objectively measured. Although there were substantial phenotypic differences among participants in weight gain, increased caloric intake, and late-night eating and fat intake, responses within participants showed stability across sleep restriction exposures. Weight change was consistent in both normal-weight and overweight adults. Weight change and increased caloric intake were more stable in men whereas late-night eating was consistent in both genders. This is the first evidence of phenotypic differential vulnerability and trait-like stability of energy balance responses to repeated sleep restriction, underscoring the need for biomarkers and countermeasures to predict and mitigate this vulnerability.
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Project description:Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin ?M (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin ?5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss.
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Project description:Shift workers, who are exposed to irregular sleep schedules resulting in sleep deprivation and misalignment of circadian rhythms, have an increased risk of diabetes relative to day workers. In healthy adults, sleep restriction without circadian misalignment promotes insulin resistance. To determine whether the misalignment of circadian rhythms that typically occurs in shift work involves intrinsic adverse metabolic effects independently of sleep loss, a parallel group design was used to study 26 healthy adults. Both interventions involved 3 inpatient days with 10-h bedtimes, followed by 8 inpatient days of sleep restriction to 5 h with fixed nocturnal bedtimes (circadian alignment) or with bedtimes delayed by 8.5 h on 4 of the 8 days (circadian misalignment). Daily total sleep time (SD) during the intervention was nearly identical in the aligned and misaligned conditions (4 h 48 min [5 min] vs. 4 h 45 min [6 min]). In both groups, insulin sensitivity (SI) significantly decreased after sleep restriction, without a compensatory increase in insulin secretion, and inflammation increased. In male participants exposed to circadian misalignment, the reduction in SI and the increase in inflammation both doubled compared with those who maintained regular nocturnal bedtimes. Circadian misalignment that occurs in shift work may increase diabetes risk and inflammation, independently of sleep loss.
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Project description:One-fourth of the human population is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) and carries the infection in its latent form. This latent infection presents a lifelong risk of developing active tuberculosis (TB) disease, and persons with latent TB infection (LTBI) are significant contributors to the pool of active TB cases. Genetic polymorphisms among hosts have been shown to contribute to the outcome of Mtb infection. The SP110 gene, which encodes an interferon-induced nuclear protein, has been shown to control host innate immunity to Mtb infection. In this study, we provide experimental data demonstrating the ability of the gene to control genetic susceptibility to latent and active TB infection. Genetic variants of the SP110 gene were investigated in the Taiwanese population (including 301 pulmonary TB patients, 68 LTBI individuals, and 278 healthy household contacts of the TB patients), and their association with susceptibility to latent and active TB infection was examined by performing an association analysis in a case-control study. We identified several SNPs (rs7580900, rs7580912, rs9061, rs11556887, and rs2241525) in the SP110 gene that are associated with susceptibility to LTBI and/or TB disease. Our studies further showed that the same SNPs may have opposite effects on the control of susceptibility to LTBI versus TB. In addition, our analyses demonstrated that the SP110 rs9061 SNP was associated with tumor necrosis factor-? (TNF?) levels in plasma in LTBI subjects. The results suggest that the polymorphisms within SP110 have a role in controlling genetic susceptibility to latent and active TB infection in humans. To the best of our knowledge, this is the first report showing that the SP110 variants are associated with susceptibility to LTBI. Our study also demonstrated that the identified SP110 SNPs displayed the potential to predict the risk of LTBI and subsequent TB progression in Taiwan.
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Project description:Local adaptations can determine the potential of populations to respond to environmental changes, yet adaptive genetic variation is commonly ignored in models forecasting species vulnerability and biogeographical shifts under future climate change. Here we integrate genomic and ecological modeling approaches to identify genetic adaptations associated with climate in two cryptic forest bats. We then incorporate this information directly into forecasts of range changes under future climate change and assessment of population persistence through the spread of climate-adaptive genetic variation (evolutionary rescue potential). Considering climate-adaptive potential reduced range loss projections, suggesting that failure to account for intraspecific variability can result in overestimation of future losses. On the other hand, range overlap between species was projected to increase, indicating that interspecific competition is likely to play an important role in limiting species' future ranges. We show that although evolutionary rescue is possible, it depends on a population's adaptive capacity and connectivity. Hence, we stress the importance of incorporating genomic data and landscape connectivity in climate change vulnerability assessments and conservation management.
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Project description:Effective inpatient teaching requires intact patient memory, but studies suggest hospitalized adults may have memory deficits. Sleep loss among inpatients could contribute to memory impairment.To assess memory in older hospitalized adults, and to test the association between sleep quantity, sleep quality, and memory, in order to identify a possible contributor to memory deficits in these patients.Prospective cohort study.General medicine and hematology/oncology inpatient wards.Fifty-nine hospitalized adults at least 50 years of age with no diagnosed sleep disorder.Immediate memory and memory after a 24-hour delay were assessed using a word recall and word recognition task from the University of Southern California Repeatable Episodic Memory Test. A vignette-based memory task was piloted as an alternative test more closely resembling discharge instructions. Sleep duration and efficiency overnight in the hospital were measured using actigraphy.Mean immediate recall was 3.8 words out of 15 (standard deviation?=?2.1). Forty-nine percent of subjects had poor memory, defined as immediate recall score of 3 or lower. Median immediate recognition was 11 words out of 15 (interquartile range [IQR]?=?9-13). Median delayed recall score was 1 word, and median delayed recognition was 10 words (IQR?=?8-12). In-hospital sleep duration and efficiency were not significantly associated with memory. The medical vignette score was correlated with immediate recall (r?=?0.49, P?<?0.01).About half of the inpatients studied had poor memory while in the hospital, signaling that hospitalization might not be an ideal teachable moment. In-hospital sleep was not associated with memory scores.
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Project description:Study objectivesSleep restriction (SR) and total sleep deprivation (TSD) reveal well-established individual differences in Psychomotor Vigilance Test (PVT) performance. While prior studies have used different methods to categorize such resiliency/vulnerability, none have systematically investigated whether these methods categorize individuals similarly.MethodsForty-one adults participated in a 13-day laboratory study consisting of two baseline, five SR, four recovery, and one 36 h TSD night. The PVT was administered every 2 h during wakefulness. Three approaches (Raw Score [average SR performance], Change from Baseline [average SR minus average baseline performance], and Variance [intraindividual variance of SR performance]), and within each approach, six thresholds (±1 standard deviation and the best/worst performing 12.5%, 20%, 25%, 33%, and 50%) classified Resilient/Vulnerable groups. Kendall's tau-b correlations examined the concordance of group categorizations of approaches within and between PVT lapses and 1/reaction time (RT). Bias-corrected and accelerated bootstrapped t-tests compared group performance.ResultsCorrelations comparing the approaches ranged from moderate to perfect for lapses and zero to moderate for 1/RT. Defined by all approaches, the Resilient groups had significantly fewer lapses on nearly all study days. Defined by the Raw Score approach only, the Resilient groups had significantly faster 1/RT on all study days. Between-measures comparisons revealed significant correlations between the Raw Score approach for 1/RT and all approaches for lapses.ConclusionThe three approaches defining vigilant attention resiliency/vulnerability to sleep loss resulted in groups comprised of similar individuals for PVT lapses but not for 1/RT. Thus, both method and metric selection for defining vigilant attention resiliency/vulnerability to sleep loss is critical.
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Project description:Individuals frequently find themselves confronted with a variety of challenges that threaten their wellbeing. While some individuals face these challenges efficiently and thrive (resilient) others are unable to cope and may suffer persistent consequences (vulnerable). Resilience/vulnerability to sleep disruption may contribute to the vulnerability of individuals exposed to challenging conditions. With that in mind we exploited individual differences in a fly's ability to form short-term memory (STM) following 3 different types of sleep disruption to identify the underlying genes. Our analysis showed that in each category of flies examined, there are individuals that form STM in the face of sleep loss (resilient) while other individuals show dramatic declines in cognitive behavior (vulnerable). Molecular genetic studies revealed that Antimicrobial Peptides, factors important for innate immunity, were candidates for conferring resilience/vulnerability to sleep deprivation. Specifically, Metchnikowin (Mtk), drosocin (dro) and Attacin (Att) transcript levels seemed to be differentially increased by sleep deprivation in glia (Mtk), neurons (dro) or primarily in the head fat body (Att). Follow-up genetic studies confirmed that expressing Mtk in glia but not neurons, and expressing dro in neurons but not glia, disrupted memory while modulating sleep in opposite directions. These data indicate that various factors within glia or neurons can contribute to individual differences in resilience/vulnerability to sleep deprivation.
| S-EPMC4416079 | biostudies-literature
Project description:Background and objectivesStress can trigger physical pain and disturb sleep. Whether dementia family caregivers experience heightened pain is unknown. Cycles of unwanted thoughts about caregiving stressors and avoidance of these thoughts-that is, caregiving-related distress-may exacerbate both pain and sleep disturbances, and genetic susceptibility to stress may further modulate these associations.Research design and methodsDementia caregivers (72 spouses, 58 adult children, ages 34-89) rated the extent to which they experienced unintended thoughts about caregiving and tried to suppress such thoughts. They also reported their pain levels, sleep problems, and depressive symptoms. Peripheral blood leukocytes were genotyped for 5-HTTLPR (serotonin-transporter-linked polymorphic region) and 5-HT1A receptor polymorphism rs6295 on the 5HTR1A locus.ResultsShort-allele carriers for 5-HTTLPR experienced more pain and sleep problems in association with greater caregiving-related distress than those with other genotypes. For rs6295, C carriers also showed the strongest links between distress and sleep problems. Those who experienced more avoidance and intrusive thoughts about caregiving had more severe depressive symptoms, consistent with past work.Discussion and implicationsCaregivers' genetic profiles helped to explain whether caregiving-related distress predicted worse pain and sleep problems. These data reveal new somatic risks of caregiver distress and provide targets for intervention. According to plasticity theories, caregivers genetically predisposed to greater stress reactivity may also respond particularly well to interventions, and many brief treatments may effectively address caregivers' intrusions and avoidance.
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