LOSS OF SLEEP CONSOLIDATION WITH AGE IN DROSOPHILA

果蝇睡眠巩固随着年龄的增长而丧失

• 批准号: 7192087
• 负责人: AMITA SEHGAL
• 金额: $ 23.66万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7192087
• 关键词: Address; Affect; Age; Aging; Aging-Related Process; Antioxidants; Behavior; Behavioral; Biological Assay; Biological Models; Caloric Restriction; Cells; Chronic; Circadian Rhythms; Condition; Coupled; Data; Deterioration; Drosophila genus; Drosophila melanogaster; Elderly; Genetic; Goals; Homeostasis; Individual; Intervention; Knowledge; Lead; Life; Light; Longevity; Longitudinal Studies; Mammals; Measures; Molecular; Monitor; Numbers; Organism; Output; Oxidative Stress; Paraquat; Pattern; Physiological; Polysomnography; Principal Investigator; Proteins; Protocols documentation; Research; Research Design; Serotonin; Serotonin Agents; Signal Transduction; Sleep; Sleep Deprivation; Sleep Disorders; Sleep Fragmentations; Sleep Wake Cycle; Stimulus; Stress; Superoxide Dismutase; Symptoms; System; Temperature; Testing; age effect; age related; base; catalase; circadian pacemaker; fly; gene therapy; light intensity; mutant; research study; response

The goal of this project is to determine the mechanisms underlying age-associated fragmentation of sleep:wake cycles and the relevance of this fragmentation to the aging process. The organism that will be used for these studies is the fruit fly,Drosophila melanogaster. In preliminary studies, we have found that the strength of the sleep:wake rhythm declines with age, such that the duration of sleep bouts decreases while the number of sleep bouts and brief awakenings increases. Using a longitudinal study design we are able to document these changes in individual Drosophila over the course of their lifespan. We have also found that an increase in oxidative stress produces changes in the sleep:wake cycle that are similar to those caused by changing; conversely, decreasing oxidative stress strengthens the cycle. We hypothesize that the deterioration of sleep:wake cycles contributes to the determination of lifespan and is caused, at least in part, by a buildup of oxidative damage. To address this hypothesis wewill: (i) Determine the relationship between sleep:wake cycle strength and lifespan. We will assay changes in sleep:wake cycles throughout life in flies with altered lifespan and test the hypothesis that these changes are associated with physiological, rather than chronological, age. (2) Examine oxidative stress as a possible mechanism for the age-related breakdown in sleep:wake cycles. We will determine how increased and decreased oxidative stress affect the changes that occur in sleep:wake cycles with age. We will also identify specific behavioral and molecular effects of oxidative stress on the sleep-regulating circadian and homeostatic systems and compare these with the effects of age. (3) Manipulate sleep and assay effects upon lifespan. We will alter environmental conditions or use genetic or pharmacological interventions to increase or decrease sleep consolidation, and assay effects upon lifespan. These experiments will indicate if sleep fragmentation contributes to the aging process. In the long-term, the knowledge gained from these studies should help to develop strategies for treating sleep problems in the elderly. Treatment ofthese problems may also alleviate other symptoms ofaging.

这个项目的目标是确定与年龄相关的碎片化的潜在机制 睡眠：觉醒周期和这种碎片化与衰老过程的相关性。这种有机体将成为 用于这些研究的是果蝇，即黑腹果蝇。在初步研究中，我们发现 睡眠强度：觉醒节律随着年龄的增长而下降，因此睡眠持续时间减少 而睡眠发作和短暂觉醒的次数则增加。使用纵向研究设计，我们 能够记录个体果蝇在其一生中的这些变化。我们还有 研究发现，氧化应激的增加会导致睡眠：觉醒周期的变化，这与 由变化引起的；相反，减少氧化应激会加强循环。我们假设 睡眠质量下降：睡眠周期决定寿命，至少部分是由睡眠周期引起的 是由于氧化损伤的积累。为了解决这一假设，我们将：(I)确定 睡眠：唤醒周期强度和寿命。我们将分析睡眠的变化：苍蝇一生中的觉醒周期 改变寿命，并测试这些变化与生理相关的假设，而不是 按时间顺序，年龄。(2)研究氧化应激作为与年龄相关的崩溃的可能机制 睡眠：唤醒周期。我们将确定氧化应激的增加和减少如何影响 发生在睡眠中：随着年龄的增长出现觉醒周期。我们还将确定特定的行为和分子效应 氧化应激对睡眠调节昼夜节律和体内平衡系统的影响，并与 年龄的影响。(3)控制睡眠并分析其对寿命的影响。我们将改变环境条件 或者使用遗传或药物干预来增加或减少睡眠巩固，以及测试效果 在生命周期上。这些实验将表明睡眠碎片是否有助于衰老过程。在……里面 从长期来看，从这些研究中获得的知识应该有助于制定治疗睡眠的策略 老年人的问题。对这些问题的治疗也可能缓解衰老的其他症状。