Mechanisms and Regulation of Neuronal Aging

神经元衰老的机制和调控

• 批准号: 9340824
• 负责人: MARC HAMMARLUND
• 金额: $ 60.63万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9340824
• 关键词: Address; Affect; Age; Aging; Axon; Binding; Biological; Biological Process; Caenorhabditis elegans; Cells; ChIP-seq; Complex; DNA Binding; Data; Defect; Exhibits; Failure; Genes; Goals; Health; Histocompatibility Testing; Human; Individual; Insulin; Insulin-Like Growth Factor Receptor; Knowledge; Life; Life Expectancy; Link; Longevity; MAP Kinase Kinase Kinase; Mediating; Mediator of activation protein; Mitochondria; Molecular; Morphology; Natural regeneration; Nervous system structure; Neurodegenerative Disorders; Neuronal Plasticity; Neurons; Organelles; Organism; Pathway interactions; Pattern; Personal Satisfaction; Predisposition; Process; Protein Isoforms; Public Health; Regulation; Research; Role; Signal Transduction; Stress; Synapses; Synaptic Transmission; Techniques; Testing; Time; Work; age effect; age related; aged; axon injury; axon regeneration; functional loss; gamma-Aminobutyric Acid; injured; injury and repair; insulin signaling; loss of function; neuron loss; neurotransmission; novel; prevent; regenerative; repaired; response; tool; trafficking; transcription factor; transcriptome sequencing

 DESCRIPTION (provided by applicant): The nervous system is highly susceptible to the effects of age. Aging affects the nervous system in specific and deleterious ways. Aging neurons are less able to repair injury, less able to transmit information, less able to maintain their normal morphology, and are more prone to degeneration and neurodegenerative disease. However, despite the clear evidence for functional loss, the molecular mechanisms that mediate neuronal aging are obscure. This proposal addresses aging within neurons-that is, how do individual neurons respond to age, and how do they regulate this response? At the same time, the ways in which neuronal aging may affect overall lifespan are investigated. The project focuses in particular on the dramatic loss of neuronal ability to repair damaged axons that occurs with age, as well as other aspects of neuronal aging. Preliminary data identify novel and specific cell-biological processes that affect neuronal aging. The project will elucidate the detailed mechanisms that contribute to neuronal aging, test their interdependence, and examine whether different functional aspects of neuronal aging are regulated by different or by common mechanisms. Each Aim is supported by extensive preliminary data, as well as by novel biological concepts and experimental approaches. Completion of these Aims will describe fundamental cellular mechanisms that mediate neuronal aging, and contribute to a more complete understanding of aging in complex organisms with multiple tissue types.

 描述（由适用提供）：神经系统非常容易受到年龄影响。衰老以特定和有害的方式影响神经系统。衰老的神经元无法修复损伤，无法传播信息，无法保持其正常形态，并且更容易发生变性和神经退行性疾病。然而，尽管有明确的功能损失证据，但介导神经元衰老的分子机制却晦涩难懂。该提案解决了神经元内的衰老 - 即单个神经元如何响应年龄，它们如何调节这种反应？同时，研究神经元衰老可能影响整体寿命的方式。该项目尤其着重于神经元能够修复随着年龄的增长以及神经元衰老的其他方面的急剧丧失。初步数据确定了广泛的初步数据以及新型的生物学概念和实验方法支持目标的新颖和特定的细胞生物学过程。这些目的的完成将描述介导神经元衰老的基本细胞机制，并有助于对具有多种组织类型的复杂生物体的衰老有更多的了解。