• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>The Journal of Neuroscience >Age-Related Phasic Patterns of Mitochondrial Maintenance in Adult Caenorhabditis elegans Neurons
【2h】

Age-Related Phasic Patterns of Mitochondrial Maintenance in Adult Caenorhabditis elegans Neurons

机译：成人秀丽隐杆线虫神经元线粒体维持的年龄相关阶段性模式。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Aging is associated with cognitive decline and increasing risk of neurodegeneration. Perturbation of mitochondrial function, dynamics, and trafficking are implicated in the pathogenesis of several age-associated neurodegenerative diseases. Despite this fundamental importance, the critical understanding of how organismal aging affects lifetime neuronal mitochondrial maintenance remains unknown, particularly in a physiologically relevant context. To address this issue, we performed a comprehensive in vivo analysis of age-associated changes in mitochondrial morphology, density, trafficking, and stress resistance in individual Caenorhabditis elegans neurons throughout adult life. Adult neurons display three distinct stages of increase, maintenance, and decrease in mitochondrial size and density during adulthood. Mitochondrial trafficking in the distal neuronal processes declines progressively with age starting from early adulthood. In contrast, long-lived daf-2 mutants exhibit delayed age-associated changes in mitochondrial morphology, constant mitochondrial density, and maintained trafficking rates during adulthood. Reduced mitochondrial load at late adulthood correlates with decreased mitochondrial resistance to oxidative stress. Revealing aging-associated changes in neuronal mitochondria in vivo is an essential precedent that will allow future elucidation of the mechanistic causes of mitochondrial aging. Thus, our study establishes the critical foundation for the future analysis of cellular pathways and genetic and pharmacological factors regulating mitochondrial maintenance in aging- and disease-relevant conditions.>SIGNIFICANCE STATEMENT Using Caenorhabditis elegans as a model, we address long-standing questions: How does aging affect neuronal mitochondrial morphology, density, trafficking, and oxidative stress resistance? Are these age-related changes amenable to genetic manipulations that slow down the aging process? Our study illustrates that mitochondrial trafficking declines progressively from the first day of adulthood, whereas mitochondrial size, density, and resistance to oxidative stress undergo three distinct stages: increase in early adulthood, maintenance at high levels during mid-adulthood, and decline during late adulthood. Thus, our study characterizes mitochondrial aging profile at the level of a single neuron in its native environment and establishes the critical foundation for the future genetic and pharmacological dissection of factors that influence long-term mitochondrial maintenance in neurons.
机译：衰老与认知能力下降和神经变性风险增加有关。线粒体功能，动力学和运输的扰动与几种年龄相关的神经退行性疾病的发病机制有关。尽管具有根本的重要性，但是关于机体衰老如何影响终生神经元线粒体维持的关键理解仍然未知，特别是在生理相关的情况下。为了解决这个问题，我们对成年秀丽隐杆线虫神经元中线粒体形态，密度，运输和应激抵抗力的年龄相关变化进行了全面的体内分析。成年神经元在成年期显示出线粒体大小和密度增加，维持和减少的三个不同阶段。从成年早期开始，随着年龄的增长，远端神经元过程中的线粒体运输逐渐减少。相比之下，长寿的daf-2突变体在线粒体形态上显示与年龄相关的延迟变化，恒定的线粒体密度，并在成年期维持贩运率。成年后期线粒体负荷减少与线粒体对氧化应激的抵抗力降低相关。揭示体内神经元线粒体中与衰老相关的变化是必不可少的先例，它将使将来阐明线粒体衰老的机理成为可能。因此，我们的研究为在衰老和疾病相关条件下调控线粒体维持的细胞途径以及遗传和药理因素的未来分析奠定了重要基础。>意义声明以秀丽隐杆线虫为模型，我们致力于长期存在的问题：衰老如何影响神经元线粒体的形态，密度，运输和抗氧化应激能力？这些与年龄相关的变化是否适合通过基因处理来减缓衰老过程？我们的研究表明，线粒体的运输从成年的第一天开始逐渐减少，而线粒体的大小，密度和对氧化应激的抵抗经历了三个不同的阶段：成年初期增加，成年中期维持在高水平以及成年后期减少。因此，我们的研究在其自然环境中表征单个神经元水平的线粒体衰老特征，并为将来影响神经元线粒体维持的因素的遗传和药理解剖奠定了重要基础。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号