Enhancing Adaptations to Exercise

我们的初步数据表明慢性炎症是导致糖尿病患者生化异常的一个因素。 肌肉和减弱一些适应性反应的运动。该项目的目的是评估 一种假说认为，慢性炎症起源于发炎的脂肪组织触发炎症 骨骼肌内的反应，导致氧化应激，线粒体能力降低， 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将确定慢性炎症对骨骼肌生理的影响。 将比较分成四分位数的老年人的骨骼肌生化和功能参数 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（TLR 4，NLRP 3），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（质谱法）。脂肪 组织炎症和衰老细胞的丰度将从皮下腹部 脂肪组织活检。功能结果将包括肌肉质量、力量、疲劳、全肌肉 氧化能力和葡萄糖代谢。安慰剂治疗24周后，将再次测量结局 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。 将在炎症四分位数中比较对单次运动的反应。行使 反应性将从肌肉蛋白质合成的诱导和假定的 转录和蛋白质组信号已知调节骨骼肌的运动适应。成果将 在安慰剂或n3-PUFA治疗24周后再次测量，以减少脂肪组织炎症。 所提出的研究的贡献预计将是一个详细的了解机制的联系 全身炎症、脂肪组织炎症和局部炎症反应之间的关系 肌肉.这项工作也将导致对慢性炎症对生化和免疫功能的影响的新见解。 老化骨骼肌的功能参数和对急性运动的反应性。获得的知识 将产生积极的影响，因为“运动阻力”是一个重要的障碍， 预防和逆转人类疾病和残疾，并了解炎症的作用 在骨骼肌生理学中的应用可能会导致新的方法来增强对运动的有益适应， 受益最多的人群。发现新的方法来提高人们的训练反应， 特别是那些有患肌肉减少症和相关代谢紊乱风险的人，将具有显著的益处， 运动无反应者患代谢性疾病的风险增加。

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.