Enhancing Adaptations to Exercise

增强运动适应能力

• 批准号: 10080916
• 负责人: IAN R LANZA
• 金额: $ 15.9万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080916
• 关键词: Abdomen; Acute; Adipose tissue; Aging; Attenuated; Biochemical; Biopsy; Blinded; Cells; Chronic; Coupling; Data; Diabetes Mellitus; Disease; Docosahexaenoic Acids; Eicosapentaenoic Acid; Elderly; Event; Exercise; Exhibits; Fatigue; Functional disorder; Gene Activation; Genetic Transcription; Goals; Heat shock proteins; Human; Impairment; Individual; Inflammation; Inflammatory; Inflammatory Response; Insulin Resistance; Interleukin-6; Intervention; Investigation; Knowledge; Lead; Link; Mass Spectrum Analysis; Measures; Messenger RNA; Metabolic; Metabolic Diseases; Mission; Mitochondria; Molecular; Mus; Muscle; Muscle Proteins; Muscle function; National Heart, Lung, and Blood Institute; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; Omega-3 Fatty Acids; Outcome; Oxidants; Oxidative Stress; Physical activity; Physiology; Placebos; Population; Prevention; Protein Biosynthesis; Proteome; Proteomics; Public Health; Research; Risk; Role; Sampling; Signal Transduction; Signaling Protein; Skeletal Muscle; TLR4 gene; TNF gene; Techniques; Testing; Therapeutic; Tracer; Training; Work; base; disability; functional disability; functional outcomes; glucose disposal; glucose metabolism; improved; inflammatory marker; insight; mitochondrial dysfunction; muscle aging; muscle form; muscle physiology; novel strategies; nutrition; oxidative damage; placebo controlled study; prevent; resistance exercise; respiratory; response; sarcopenia; senescence; subcutaneous

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，慢性炎症可能是导致脑血管疾病生化异常的一个因素。 并减弱对运动的一些适应性反应。该项目的目标是评估 一种假说认为慢性炎症源于发炎的脂肪组织会引发炎症 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。 目的1确定慢性炎症对骨骼肌生理的影响。 骨骼肌生化和功能参数将被分成四分位数的老年人进行比较 基于综合全身炎症评分。肌肉活组织检查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、 偶联效率)，以及对肌肉蛋白质组质量的影响(质谱学)。脂肪 组织炎症和衰老细胞的丰度将从皮下腹部确定 脂肪组织活组织检查。功能结果将包括肌肉质量、力量、疲劳、整个肌肉 氧化能力和葡萄糖代谢。在服用安慰剂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)，以减轻脂肪组织炎症。 目标2将确定慢性炎症对急性运动反应的影响。 对一次运动的反应性将在炎症四分位数之间进行比较。锻炼 反应性将通过肌肉蛋白质合成的诱导和假定的变化来确定 已知的转录和蛋白质组信号调节骨骼肌中的运动适应。结果将会 在服用安慰剂或n3-PUFAs 24周后再次测量，以减少脂肪组织炎症。 预计拟议研究的贡献将是对机制联系的详细理解 衰老中全身炎症、脂肪组织炎症和局部炎症反应之间的关系 肌肉。这项工作还将导致对慢性炎症对生化和免疫功能影响的新见解。 衰老骨骼肌的功能参数和对急性运动的反应。所获得的知识 这项研究将产生积极的影响，因为“运动阻力”是一大障碍。 对人类疾病和残疾的预防和逆转，以及了解炎症的作用 可能导致新的方法来增强对运动的有益适应 受益最大的人群。发现增强人们训练反应的新方法， 特别是那些有骨质疏松症和相关代谢紊乱风险的人，将会有很大的好处，因为 没有运动反应的人患代谢性疾病的风险会增加。