Enhancing Adaptations to Exercise

增强运动适应能力

基本信息

  • 批准号:
    10399404
  • 负责人:
  • 金额:
    $ 62.47万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-01 至 2024-04-30
  • 项目状态:
    已结题

项目摘要

Our preliminary data implicates chronic inflammation as a factor that may lead to biochemical abnormalities in muscle and attenuate some of the adaptive responses to exercise. The objective of this project is to evaluate a hypothesis that chronic inflammation originating from inflamed adipose tissue triggers inflammatory responses within skeletal muscle, leading to oxidative stress, reduced mitochondrial capacity, compromised muscle quality, functional and metabolic impairments, and attenuated adaptive responses to exercise. Aim 1 will determine the impact of chronic inflammation on skeletal muscle physiology. Skeletal muscle biochemical and functional parameters will be compared in older adults grouped into quartiles based on a composite systemic inflammatory score. Muscle biopsies will be used to evaluate muscle-specific inflammatory responses (TLR4, NLRP3), mitochondrial function (respiratory capacity, oxidant emissions, coupling efficiency), and the impact on the quality of the muscle proteome (mass spectrometry). Adipose tissue inflammation and abundance of senescent cells will be determined from subcutaneous abdominal adipose tissue biopsies. Functional outcomes will include muscle mass, strength, fatigue, whole-muscle oxidative capacity, and glucose metabolism. Outcomes will be measured again following 24 weeks of placebo or eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA) to reduce adipose tissue inflammation. Aim 2 will determine the impact of chronic inflammation on responsiveness to acute exercise. Responsiveness to a single bout of exercise will be compared across inflammation quartiles. Exercise responsiveness will be determined from the induction of muscle protein synthesis and changes in putative transcriptional and proteomic signals known to regulate exercise adaptations in skeletal muscle. Outcomes will be measured again following 24 weeks of placebo or n3-PUFAs to reduce adipose tissue inflammation. The contribution of the proposed research is expected to be a detailed understanding of the mechanistic links between systemic inflammation, adipose tissue inflammation, and local inflammatory responses within aging muscle. This work will also lead to new insights into the influence of chronic inflammation on biochemical and functional parameters in aging skeletal muscle and responsiveness to acute exercise. The knowledge gained in the proposed study will have a positive impact because “exercise resistance” represents a significant barrier to the prevention and reversal of disease and disability in humans, and understanding the role of inflammation in skeletal muscle physiology may lead to new approaches to enhance the beneficial adaptations to exercise in populations that stand to benefit most. Discovering new ways to enhance training responses in people, particularly those at risk for sarcopenia and related metabolic disorders, will have significant benefit since exercise non-responders have increased risk for metabolic disease.
我们的初步数据表明慢性炎症是可能导致生化异常的一个因素 肌肉并减弱一些对运动的适应性反应。该项目的目标是评估 一种假设,即源自发炎脂肪组织的慢性炎症会引发炎症 骨骼肌内的反应,导致氧化应激、线粒体能力降低、受损 肌肉质量、功能和代谢损伤以及对运动的适应性反应减弱。 目标 1 将确定慢性炎症对骨骼肌生理学的影响。 将按四分位数分组的老年人的骨骼肌生化和功能参数进行比较 基于综合全身炎症评分。肌肉活检将用于评估肌肉特异性 炎症反应(TLR4、NLRP3)、线粒体功能(呼吸能力、氧化剂排放、 耦合效率),以及对肌肉蛋白质组质量(质谱)的影响。脂肪 组织炎症和衰老细胞的丰度将从腹部皮下确定 脂肪组织活检。功能结果包括肌肉质量、力量、疲劳、全肌肉 氧化能力和葡萄糖代谢。使用安慰剂 24 周后将再次测量结果 或二十碳五烯酸+二十二碳六烯酸(EPA+DHA)以减少脂肪组织炎症。 目标 2 将确定慢性炎症对急性运动反应的影响。 将比较炎症四分位数对单次运动的反应。锻炼 反应性将由肌肉蛋白质合成的诱导和假定的变化来确定 已知调节骨骼肌运动适应的转录和蛋白质组信号。结果将 在使用安慰剂或 n3-PUFA 24 周以减少脂肪组织炎症后再次测量。 拟议研究的贡献预计是对机制联系的详细理解 衰老过程中全身炎症、脂肪组织炎症和局部炎症反应之间的关系 肌肉。这项工作还将带来关于慢性炎症对生化和代谢的影响的新见解。 衰老骨骼肌的功能参数和对急性运动的反应。获得的知识 在拟议的研究中将会产生积极的影响,因为“运动阻力”是一个重大障碍 预防和逆转人类疾病和残疾,并了解炎症的作用 骨骼肌生理学中的研究可能会带来新的方法来增强对运动的有益适应 受益最多的人群。发现增强人们训练反应的新方法, 特别是那些有肌肉减少症和相关代谢紊乱风险的人,将获得显着的益处,因为 运动无反应者患代谢疾病的风险增加。

项目成果

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IAN R LANZA其他文献

IAN R LANZA的其他文献

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{{ truncateString('IAN R LANZA', 18)}}的其他基金

Exercise Response in Humans with Obesity
肥胖症患者的运动反应
  • 批准号:
    10659320
  • 财政年份:
    2023
  • 资助金额:
    $ 62.47万
  • 项目类别:
Mayo Clinic Undiagnosed Disease Network Metabolomics Core
梅奥诊所未确诊疾病网络代谢组学核心
  • 批准号:
    10600558
  • 财政年份:
    2022
  • 资助金额:
    $ 62.47万
  • 项目类别:
Mayo Clinic Undiagnosed Disease Network Metabolomics Core
梅奥诊所未确诊疾病网络代谢组学核心
  • 批准号:
    9750262
  • 财政年份:
    2018
  • 资助金额:
    $ 62.47万
  • 项目类别:
Mayo Clinic Undiagnosed Disease Network Metabolomics Core
梅奥诊所未确诊疾病网络代谢组学核心
  • 批准号:
    10213162
  • 财政年份:
    2018
  • 资助金额:
    $ 62.47万
  • 项目类别:
Mayo Clinic Undiagnosed Disease Network Metabolomics Core
梅奥诊所未确诊疾病网络代谢组学核心
  • 批准号:
    9982453
  • 财政年份:
    2018
  • 资助金额:
    $ 62.47万
  • 项目类别:
Enhancing Adaptations to Exercise
增强对运动的适应
  • 批准号:
    9692669
  • 财政年份:
    2017
  • 资助金额:
    $ 62.47万
  • 项目类别:
Enhancing Adaptations to Exercise
增强运动适应能力
  • 批准号:
    10080916
  • 财政年份:
    2017
  • 资助金额:
    $ 62.47万
  • 项目类别:
Mayo Clinic Physical Activity Research Center: Metabolomics and Proteomics Analysis Site
梅奥诊所体育活动研究中心:代谢组学和蛋白质组学分析网站
  • 批准号:
    9516276
  • 财政年份:
    2016
  • 资助金额:
    $ 62.47万
  • 项目类别:
Mayo Clinic Physical Activity Research Center: Metabolomics and Proteomics Analysis Site
梅奥诊所体育活动研究中心:代谢组学和蛋白质组学分析网站
  • 批准号:
    9245805
  • 财政年份:
    2016
  • 资助金额:
    $ 62.47万
  • 项目类别:
Mayo Clinic Physical Activity Research Center: Metabolomics and Proteomics Analysis Site
梅奥诊所体育活动研究中心:代谢组学和蛋白质组学分析网站
  • 批准号:
    10320026
  • 财政年份:
    2016
  • 资助金额:
    $ 62.47万
  • 项目类别:

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Acute and Chronic Effects of Adipose Tissue Growth on Cellular and Metabolic Processes
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Acute and Chronic Effects of Adipose Tissue Growth on Cellular and Metabolic Processes
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  • 批准号:
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