Exploring links between circadian clocks and aging.

探索生物钟与衰老之间的联系。

• 批准号: 8030253
• 负责人: Jadwiga M Giebultowicz
• 金额: $ 14.55万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8030253
• 关键词: Address; Affect; Age; Aging; Animal Model; Behavior; Biological; Biological Markers; Circadian Rhythms; Clock protein; Data; Defect; Drosophila genus; Drosophila melanogaster; Gene Expression; Genes; Goals; Health; Homeostasis; Human; Individual; Knowledge; Laboratories; Lead; Life; Limb structure; Link; Longevity; Malignant Neoplasms; Mammals; Metabolism; Modeling; Molecular; Nature; Neurodegenerative Disorders; Organism; Outcome; Pathology; Pathway interactions; Phosphorylation; Physiological; Physiology; Play; Premature aging syndrome; Property; Research; Research Proposals; Role; Societies; System; Testing; Transgenic Organisms; Western Blotting; Work; age related; aged; anti aging; circadian pacemaker; cognitive function; fly; gene therapy; genetic manipulation; healthy aging; improved; innovation; insight; novel; premature; repaired; research study; stressor; Address; Affect; Age; Aging; Animal Model; Behavior; Biological; Biological Markers; Circadian Rhythms; Clock protein; Data; Defect; Drosophila genus; Drosophila melanogaster; Gene Expression; Genes; Goals; Health; Homeostasis; Human; Individual; Knowledge; Laboratories; Lead; Life; Limb structure; Link; Longevity; Malignant Neoplasms; Mammals; Metabolism; Modeling; Molecular; Nature; Neurodegenerative Disorders; Organism; Outcome; Pathology; Pathway interactions; Phosphorylation; Physiological; Physiology; Play; Premature aging syndrome; Property; Research; Research Proposals; Role; Societies; System; Testing; Transgenic Organisms; Western Blotting; Work; age related; aged; anti aging; circadian pacemaker; cognitive function; fly; gene therapy; genetic manipulation; healthy aging; improved; innovation; insight; novel; premature; repaired; research study; stressor

DESCRIPTION (provided by applicant): Exploring links between circadian clocks and aging Summary: Age-related decline in the physiological and cognitive functions in humans is of great concern to society and there is an urgent need to identify the biological mechanisms that support healthy aging and longevity. Recent evidence suggests that the biological (circadian) clocks are important for maintaining health during aging. Circadian clocks are endogenous molecular regulators that coordinate daily changes in the level of gene expression, physiological functions and behavior with external day/night cycles. Disruption of circadian clocks in mammals result in accelerated aging and increased age-related pathologies such as cancer and neurodegenerative diseases. Data from our laboratory demonstrated that disruption of circadian clock in the model organism Drosophila melanogaster also leads to premature aging and compromised longevity. The aim of this proposal is to test the hypothesis that deregulation of circadian network is causally linked to aging in Drosophila. We plan to investigate the relationship between circadian systems and aging by focusing on two aims: a) we will attempt to increase the expression of declining clock genes via transgenic manipulations, and determine whether these treatments can enhance the amplitude of per and tim circadian oscillations in old flies. This will allow us to identify the molecular defects that cause age-related decay of circadian network and help us attempt to reverse this decay by genetic interventions b) Test if high amplitude of circadian oscillations support longevity and health during aging. Our results should provide critical information regarding links between strong circadian clocks and longevity. The fruitfly Drosophila is an excellent model to address these links due to its short lifespan (~60 days) and conservation of clock genes and aging mechanisms between flies and humans. Insights obtained from this innovative exploratory research will lead to a better understanding of the mechanisms that link rhythmic oscillations of the circadian system with health and longevity. The outcomes of this exploratory research proposal may point to novel ways to maintain optimal health during aging in humans by enhancement of the circadian systems. PUBLIC HEALTH RELEVANCE: Age-related decline in various life functions in humans is of great concern for society, and there is an urgent need to identify the biological mechanisms that support healthy aging and longevity. Recent evidence suggests that the biological (circadian) clocks play important roles in maintaining health during aging. The proposed studies will uncover the molecular mechanisms that cause age related decay of the circadian clock mechanism. Insights obtained from this work performed on a model organism may lead to novel ways of increasing longevity in humans by enhancing the circadian clock amplitude in aging individuals.

描述（由申请人提供）：探索昼夜节律与老化摘要之间的联系：与人类的生理和认知功能相关的年龄相关的下降是社会的极大关注，并且迫切需要确定支持健康衰老和寿命的生物学机制。最近的证据表明，生物（昼夜节律）时钟对于在衰老过程中保持健康很重要。昼夜节律时钟是内源性分子调节剂，可以通过外部白天/夜间周期来协调基因表达，生理功能和行为水平的每日变化。哺乳动物中昼夜节律时钟的破坏会导致衰老加速，并增加与年龄相关的病理，例如癌症和神经退行性疾病。我们实验室的数据表明，模型有机体中昼夜节律时钟的破坏也导致过早衰老和寿命损害。该提议的目的是检验以下假设：昼夜节律网络的放松管制与果蝇的衰老有因果关系。我们计划通过关注两个目的来研究昼夜节律系统与衰老之间的关系：a）我们将尝试通过转基因操作来增加时钟基因下降的表达，并确定这些治疗方法是否可以增强旧蝇中PER和TIM昼夜节律振荡的幅度。这将使我们能够确定引起年龄相关的昼夜节律衰减的分子缺陷，并帮助我们试图通过遗传干预措施来扭转这种衰变b）测试昼夜节律振荡是否支持衰老期间的寿命和健康。我们的结果应提供有关强烈昼夜节律与寿命之间联系的关键信息。果蝇果蝇是一个很好的模型，可以解决这些联系，因为其寿命短（约60天）以及苍蝇和人之间的时钟基因和老化机制的保存。从这项创新的探索性研究中获得的见解将使人们对将昼夜节律系统的节奏振荡与健康和寿命联系起来的机制有了更好的了解。这项探索性研究建议的结果可能指出了通过增强昼夜节律系统在人类衰老期间保持最佳健康的新方法。 公共卫生相关性：人类各种生活功能的年龄相关性下降对社会引起了极大关注，并且迫切需要确定支持健康衰老和寿命的生物学机制。最近的证据表明，生物学（昼夜节律）时钟在维持衰老期间保持健康方面起着重要作用。拟议的研究将发现导致年龄相关的昼夜节律机制的分子机制。从模型生物体上进行的这项工作中获得的见解可能会通过增强衰老个体的昼夜节律时钟幅度来增加人类寿命的新方法。