The role of type 2 diabetes on skeletal muscle atrophy and recovery following bed rest in older adults

2 型糖尿病对老年人卧床休息后骨骼肌萎缩和恢复的作用

基本信息

  • 批准号:
    10231270
  • 负责人:
  • 金额:
    $ 70.33万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-01 至 2023-05-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Loss of muscle mass during periods of disuse due to illness or hospitalization and poor recovery have serious health consequences for older adults. The mechanisms underlying the atrophy response to disuse and subsequent recovery in humans, however, are not known. We posit that poor mitochondrial energetics and altered muscle lipid metabolism contribute to greater disuse- induced muscle atrophy and poor recovery. In addition, we believe that older subjects with type 2 diabetes have reduced mitochondria capacity and excess muscle lipids, which exacerbates the deleterious effect of bed rest on muscle mass and impairs recovery. Mitochondria play a fundamental role in muscle health and impaired mitochondrial energetics and muscle lipids have been shown to contribute to human aging and type 2 diabetes. The role of mitochondrial energetics in human muscle atrophy and recovery is not known. In this project, we will test the hypothesis that altered mitochondrial energetics in muscle atrophy and recovery via cardiolipin remodeling, elevated reactive oxygen species (ROS) emission and accumulation of specific muscle sphingolipids blunt anabolic stimuli and contribute to muscle atrophy and poor recovery. The overall objective of this project is to decipher mechanisms by which mitochondrial energetics and muscle lipids underlie early muscle catabolic and anabolic responses to disuse and recovery. Studying older adults with type 2 diabetes and using an exercise recovery program will provide a physiological context and will allow us to delineate novel mechanisms. Through innovative time course studies and measurements in serial human muscle biopsies, we will place the etiology of muscle atrophy firmly in the context of mitochondrial biology and will contribute to a better precision medicine approach to prevent and treat disuse atrophy.
项目摘要 在因疾病或住院而废用期间肌肉质量的损失以及恢复不良, 对老年人的健康影响。废用性萎缩反应的潜在机制, 然而,随后在人类中的恢复尚不清楚。 我们认为,线粒体能量学和肌肉脂质代谢的改变导致了更大的废用- 导致肌肉萎缩和恢复不良。此外,我们认为老年2型糖尿病患者 线粒体容量减少,肌肉脂质过多,加剧了卧床的有害影响。 停留在肌肉质量上并损害恢复。 线粒体在肌肉健康和受损的线粒体能量学和肌肉脂质中起着重要作用 已经被证明会导致人类衰老和2型糖尿病。线粒体能量学在 人类肌肉萎缩和恢复是未知的。在这个项目中,我们将测试的假设,改变了 肌萎缩和通过心磷脂重塑恢复中的线粒体能量学,活性氧升高 种(ROS)的排放和积累特定的肌肉鞘脂钝合成代谢刺激, 导致肌肉萎缩和恢复不良。 该项目的总体目标是破译线粒体能量学和肌肉 脂质是肌肉对废用和恢复的早期分解代谢和合成代谢反应的基础。研究老年人 2型糖尿病患者和使用运动恢复计划将提供一个生理背景, 我们描绘新的机制。通过创新的时间过程研究和测量, 肌肉活检,我们将把肌肉萎缩的病因学牢牢地放在线粒体生物学的背景下, 将有助于更好的精准医学方法来预防和治疗废用性萎缩。

项目成果

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Paul Martin Coen其他文献

Paul Martin Coen的其他文献

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{{ truncateString('Paul Martin Coen', 18)}}的其他基金

Impact of mitochondrial genetics on muscle oxidative capacity, fitness, and mobility in older adults
线粒体遗传学对老年人肌肉氧化能力、健康和活动能力的影响
  • 批准号:
    10705262
  • 财政年份:
    2022
  • 资助金额:
    $ 70.33万
  • 项目类别:
Impact of mitochondrial genetics on muscle oxidative capacity, fitness, and mobility in older adults
线粒体遗传学对老年人肌肉氧化能力、健康和活动能力的影响
  • 批准号:
    10522044
  • 财政年份:
    2022
  • 资助金额:
    $ 70.33万
  • 项目类别:
BAT as a therapeutic for the metabolic and cardiac dysfunction with senescence.
BAT 作为治疗衰老代谢和心脏功能障碍的药物。
  • 批准号:
    10355418
  • 财政年份:
    2019
  • 资助金额:
    $ 70.33万
  • 项目类别:
BAT as a therapeutic for the metabolic and cardiac dysfunction with senescence.
BAT 作为治疗衰老代谢和心脏功能障碍的药物。
  • 批准号:
    10557231
  • 财政年份:
    2019
  • 资助金额:
    $ 70.33万
  • 项目类别:
BAT as a therapeutic for the metabolic and cardiac dysfunction with senescence.
BAT 作为治疗衰老代谢和心脏功能障碍的药物。
  • 批准号:
    10092058
  • 财政年份:
    2019
  • 资助金额:
    $ 70.33万
  • 项目类别:
The role of type 2 diabetes on skeletal muscle atrophy and recovery following bed rest in older adults
2 型糖尿病对老年人卧床休息后骨骼肌萎缩和恢复的作用
  • 批准号:
    10412070
  • 财政年份:
    2018
  • 资助金额:
    $ 70.33万
  • 项目类别:
The role of type 2 diabetes on skeletal muscle atrophy and recovery following bed rest in older adults
2 型糖尿病对老年人卧床休息后骨骼肌萎缩和恢复的作用
  • 批准号:
    9765131
  • 财政年份:
    2018
  • 资助金额:
    $ 70.33万
  • 项目类别:
Ceramide Mediated Oxidative Stress in Muscle Loss with Aging and Disuse
神经酰胺介导的氧化应激导致衰老和废用性肌肉损失
  • 批准号:
    8727434
  • 财政年份:
    2013
  • 资助金额:
    $ 70.33万
  • 项目类别:
Ceramide Mediated Oxidative Stress in Muscle Loss with Aging and Disuse
神经酰胺介导的氧化应激导致衰老和废用性肌肉损失
  • 批准号:
    8867115
  • 财政年份:
    2013
  • 资助金额:
    $ 70.33万
  • 项目类别:
Ceramide Mediated Oxidative Stress in Muscle Loss with Aging and Disuse
神经酰胺介导的氧化应激导致衰老和废用性肌肉损失
  • 批准号:
    8486746
  • 财政年份:
    2013
  • 资助金额:
    $ 70.33万
  • 项目类别:

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急性和慢性 GPCR 药物心脏保护:受体串扰的作用、细胞信号传导以及年龄的影响
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