The relationship between blood based bioenergetics and muscle function, mobility, and aging

基于血液的生物能学与肌肉功能、活动能力和衰老之间的关系

• 批准号: 10363365
• 负责人: ANTHONY J MOLINA
• 金额: $ 68.94万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10363365
• 关键词: Age; Aging; Ancillary Study; Biochemical; Bioenergetics; Biological Assay; Biological Markers; Biology; Biopsy; Blood; Blood Cells; Blood Platelets; Brain; Cardiovascular system; Cells; Chemicals; Clinical; Complex; Coupled; Data; Denervation; Elderly; Electron Transport; Enrollment; Fatty Acids; Functional disorder; Genus Hippocampus; Glucose; Glycerophosphates; Glycolysis; Health Care Costs; Healthcare; Heart; Heterogeneity; Human; Individual; Knowledge; Lead; Link; Longitudinal Studies; Longitudinal prospective study; Lung; Measurement; Measures; Mediator of activation protein; Methodology; Methods; Mitochondria; Molecular Analysis; Morbidity - disease rate; Muscle; Muscle Mitochondria; Muscle function; Musculoskeletal; Myocardium; Neuraxis; Organ; Outcome; Oxidative Phosphorylation; Parents; Participant; Performance; Peripheral Blood Mononuclear Cell; Persons; Physical Function; Physical Performance; Play; Population; Production; Quality of life; Research; Resolution; Role; Schedule; Site; Skeletal Muscle; Solid; System; Testing; Time; Tissues; Visit; Walking; age related; aged; aging population; base; body system; cohort; cost effective; experience; extracellular; follow-up; mitochondrial dysfunction; mortality; muscle form; novel; sarcopenia; therapy development

As people age, they experience declining physical performance, which is associated with diminished quality of life, augmented health care costs, and is a strong predictor of morbidity and mortality. Thus, uncovering mechanisms that underlie age-associated mobility decline and identifying reliable biomarkers to predict this decline is imperative for the development of interventions to maintain physical ability with age. Mitochondria generate chemical energy to support homeostatic function of most cells in the body, and mitochondrial dysfunction is linked to age-associated decline in physical performance. This has been studied predominantly in skeletal muscle mitochondria since muscle function is central to physical ability. However, it is recognized that muscle function is not the sole determinant of mobility, and that input from other organ systems (cardiovascular and central nervous system) is also required. While age associated mitochondrial dysfunction has been observed across all organ systems, the contribution of this systemic bioenergetic dysfunction to age-associated mobility decline has not been assessed. The current study brings together two PIs with expertise in mitochondrial biology who have independently optimized and validated complementary assays (high resolution respirometery and Seahorse extracellular flux analysis) for the measurement of systemic bioenergetic function utilizing blood cells (platelets and peripheral blood mononuclear cells). Preliminary data using these assays show that blood cell mitochondrial function reflects bioenergetics of solid tissues (e.g. skeletal muscle, heart, lung, brain) and correlates with multiple measures of physical ability. However, it is unknown whether blood cell bioenergetics reflect skeletal muscle function or are predictive of mobility decline in older adults. The Study of Muscle, Mobility and Aging (SOMMA) is a multi-site longitudinal study of older adults (≥70 years; n=875). SOMMA focuses on the relationship between skeletal muscle mitochondria and mobility decline and will obtain skeletal muscle biopsies to measure mitochondrial function in all participants. Physical performance measures will at baseline and three years follow-up. The current proposal is an ancillary study that synergizes with SOMMA to add blood cell bioenergetic measurements in all SOMMA participants at baseline as well as at the three year follow up visit. Using these data, we will test whether blood cell bioenergetics are 1) reflective of skeletal muscle mass and function, 2) are associated with physical performance measures (400 m walk), and 3) are predictive of physical performance decline in older adults. Completion of this study will elucidate systemic mitochondrial changes that are associated with age-related physical decline, and potentially establish blood cell bioenergetics as a biomarker of systemic mitochondrial function that can be utilized as a surrogate for muscle biopsies, and as a predictor of mobility decline in the aging population.

随着人们的年龄，他们的身体表现会下降，这与降低有关 生活质量，增强医疗保健成本，是发病率和死亡率的有力预测指标。那， 发现与年龄相关的流动性下降并确定可靠的生物标志物的机制 预测这种下降对于发展干预措施以保持身体能力的发展至关重要 年龄。线粒体产生化学能以支持体内大多数细胞的稳态功能， 线粒体功能障碍与年龄相关的身体性能下降有关。这是 由于肌肉功能对身体能力至关重要，因此主要在骨骼肌线粒体中进行研究。 但是，人们认识到肌肉功能不是移动性的唯一决定者，而是从 还需要其他器官系统（心血管和中枢神经系统）。而年龄相关 在所有器官系统中都观察到了线粒体功能障碍，这是该系统性的贡献 尚未评估与年龄相关的流动性下降的生物能功能障碍。当前的研究 汇集了两个PI具有独立优化和线粒体生物学专业知识的PI 经过验证的完成分析（高分辨率呼​​吸计和海马细胞外通量分析） 用于使用血细胞（血小板和外周血）测量全身生物能功能 单核细胞）。使用这些测定的初步数据表明血细胞线粒体功能 反映固体组织（例如骨骼肌，心脏，肺，大脑）的生物能学，并与多个 身体能力的度量。但是，尚不清楚血细胞生物能是否反映骨骼 肌肉功能或预测老年人的流动性下降。肌肉，流动性和 衰老（SOMMA）是一项对老年人的多部位纵向研究（≥70岁； n = 875）。 Somma专注于 骨骼肌线粒体与迁移率下降之间的关系，将获得骨骼 肌肉活检以测量所有参与者的线粒体功能。身体绩效措施 将在基线和三年后续行动。当前的建议是一项辅助研究，与 在基线和所有SOMMA参与者中以及 在三年后续访问中。使用这些数据，我们将测试血细胞生物能是否为1） 反映骨骼肌质量和功能，2）与身体表现措施有关 （步行400 m）和3）可以预测老年人的身体表现下降。完成此操作 研究将阐明与年龄相关的身体下降相关的全身线粒体变化， 并有可能确定血细胞生物能作为系统性线粒体功能的生物标志物 可以用作肌肉活检的替代物，也可以用作衰老的流动性下降的预测指标 人口。