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

基本信息

批准号：
10569677
负责人：
ANTHONY J MOLINA
金额：
$ 62.61万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
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/10569677
关键词：
Age Aging Ancillary Study Biochemical Bioenergetics Biological Assay Biological Markers Biology Biopsy Blood Blood Cells Blood Platelets Brain Cardiovascular system Cells Central Nervous System 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 Lung Measurement Measures Mediator Methodology Methods Mitochondria Molecular Analysis Morbidity - disease rate Muscle Muscle Mitochondria Muscle function Musculoskeletal Myocardium Organ Outcome Oxidative Phosphorylation Parents Participant Performance Peripheral Blood Mononuclear Cell Permeability Persons Physical Function Physical Performance Play Population Production Quality of life Research Resolution Role Schedule Site Skeletal Muscle Solid Spirometry System Testing Time Tissues Visit Walking age related aged aging population body system cohort cost effective experience extracellular follow-up longitudinal, prospective study mitochondrial dysfunction mortality muscle form novel sarcopenia synergism therapy development

项目摘要

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，他们的身体机能会下降，这与能力下降有关生活质量、增加的医疗保健费用，并且是发病率和死亡率的有力预测因素。揭示与年龄相关的行动能力下降的机制并确定可靠的生物标志物预测这种下降对于制定干预措施以维持身体能力至关重要线粒体产生化学能来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机能下降有关。主要研究骨骼肌线粒体，因为肌肉功能是身体能力的核心。然而，人们认识到肌肉功能并不是活动能力的唯一决定因素，并且来自其他器官系统（心血管和中枢神经系统）也需要，而年龄则与年龄相关。在所有器官系统中都观察到线粒体功能障碍，这种系统性的贡献目前的研究尚未评估生物能量功能障碍与年龄相关的活动能力下降。汇集了两位具有线粒体生物学专业知识的 PI，他们独立优化和经过验证的补充测定（高分辨率呼吸计和 Seahorse 细胞外通量分析）用于利用血细胞（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。反映实体组织（例如骨骼肌、心脏、肺、脑）的生物能，并与多种相关然而，尚不清楚血细胞生物能是否反映骨骼。肌肉功能或可预测老年人的活动能力下降。老龄化 (SOMMA) 是一项针对老年人（≥70 岁；n=875）的多中心纵向研究。骨骼肌线粒体与活动能力下降的关系，将获得骨骼肌肌肉活检以测量所有参与者的线粒体功能。将在基线和三年随访中进行当前的提案是一项与其他研究相协同的辅助研究。 SOMMA 将为所有 SOMMA 参与者添加基线和血细胞生物能测量在三年的随访中，我们将使用这些数据测试血细胞生物能是否为 1)。反映骨骼肌质量和功能，2) 与身体表现指标相关（400 m 步行）和 3) 预示着老年人完成此任务后身体机能会下降。研究将阐明与年龄相关的身体衰退相关的全身线粒体变化，并建立潜在的血细胞生物能量学作为全身线粒体功能的生物标志物可用作肌肉活检的替代品，并作为衰老过程中活动能力下降的预测指标人口。