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.

随着人们年龄的增长，他们的体能表现会下降，这与衰退有关 生活质量、增加的医疗保健费用，是发病率和死亡率的有力预测因素。因此， 揭示年龄相关性流动性下降的机制并确定可靠的生物标志物 预测这一下降对于制定干预措施以维持体能是必不可少的 年龄。线粒体产生化学能量来支持体内大多数细胞的动态平衡功能， 线粒体功能障碍与年龄相关的体能下降有关。这已经是 主要在骨骼肌线粒体进行研究，因为肌肉功能是体能的核心。 然而，人们认识到，肌肉功能并不是行动能力的唯一决定因素，而来自 其他器官系统(心血管和中枢神经系统)也是必需的。当年龄关联时 已经观察到所有器官系统的线粒体功能障碍，这是系统性的贡献 生物能量功能障碍与年龄相关性活动能力下降之间的关系尚未得到评估。目前的研究 汇集了两名在线粒体生物学方面具有专业知识的PI，他们独立优化和 有效的补充分析(高分辨率呼吸测定仪和海马细胞外通量分析) 利用血细胞(血小板和外周血液)测量全身生物能量功能 单个核细胞)。使用这些检测的初步数据显示，血细胞线粒体功能 反映固体组织(例如骨骼肌、心脏、肺、脑)的生物能量学，并与 体能的衡量标准。然而，血细胞生物能量学是否反映骨骼尚不清楚。 肌肉功能或预测老年人的行动能力下降。肌肉、活动能力和运动能力的研究 老龄化(SOMA)是一项针对老年人的多点纵向研究(≥70年；n=875)。Somma专注于 骨骼肌线粒体数与运动能力下降及骨骼发育的关系 肌肉活检以测量所有参与者的线粒体功能。体能表现衡量标准 将在基线和三年内进行随访。目前的建议是一项辅助研究，它与 Somma将在所有Somma参与者中添加基线血细胞生物能量测量以及 在三年的随访中。使用这些数据，我们将测试血细胞生物能量学是否1) 反映骨骼肌质量和功能，2)与体能测量相关 (400米步行)，以及3)是老年人体能下降的预测因素。完成这项工作 这项研究将阐明与年龄相关的身体衰退相关的系统性线粒体变化， 并有可能建立血细胞生物能量学作为系统线粒体功能的生物标记物 可以作为肌肉活组织检查的替代指标，也可以作为老年人活动能力下降的预测指标 人口。