LOSS OF SLEEP CONSOLIDATION WITH AGE IN DROSOPHILA

果蝇睡眠巩固随着年龄的增长而丧失

基本信息

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
项目类别：
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

项目摘要

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.

该项目的目标是确定与年龄相关的碎片的潜在机制睡眠：觉醒周期以及这种碎片与衰老过程的相关性。将会成为的有机体用于这些研究的是果蝇，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，从而导致睡眠持续时间减少同时睡眠和短暂觉醒的次数增加。使用纵向研究设计，我们能够记录果蝇个体在其一生中的这些变化。我们还有发现氧化应激的增加会导致睡眠：觉醒周期的变化，与这些变化类似因改变而引起的；相反，减少氧化应激会加强循环。我们假设睡眠恶化：觉醒周期有助于确定寿命，并且至少部分是由于，通过氧化损伤的积累。为了解决这个假设，我们将：（i）确定之间的关系睡眠：觉醒周期强度和寿命。我们将分析果蝇一生中睡眠的变化：觉醒周期寿命改变并检验这些变化与生理相关而不是与生理相关的假设按时间顺序，年龄。 (2) 研究氧化应激作为与年龄相关的衰老的可能机制睡眠：觉醒周期。我们将确定氧化应激的增加和减少如何影响以下变化：发生在睡眠中：随年龄的觉醒周期。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稳态系统的影响，并将其与年龄的影响。 (3) 操纵睡眠和测定对寿命的影响。我们将改变环境条件或使用遗传或药物干预来增加或减少睡眠巩固和测定效果取决于寿命。这些实验将表明睡眠碎片化是否会导致衰老过程。在从长远来看，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。治疗这些问题还可以缓解其他衰老症状。