Aging Mitochondrial Fragmentation and Metabolic Inflexibility

衰老线粒体碎片和代谢不灵活

基本信息

批准号：
9901270
负责人：
GEORGE Austin BROOKS
金额：
$ 6.62万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9901270
关键词：
Adipocytes Adipose tissue Affect Age Aging Biopsy Blood Carbohydrates Cell Line Cells Closure by clamp Complement Dietary Fats Energy-Generating Resources Exercise Fat emulsion Fatty acid glycerol esters Female Gene Expression Generations Glucose Glycerol Harvest Heparin Human Inbred F344 Rats Individual Infusion procedures Insulin Resistance Intravenous infusion procedures Isotopes Knock-out Knockout Mice Lipid Mobilization Lipids Lipolysis Metabolic Mitochondria Mus Muscle Cells Muscle Mitochondria Muscular Atrophy Nonesterified Fatty Acids OGTT Organelles Output Palmitates Pharmaceutical Preparations Physical Fitness Physical activity Physiological Population Preparation Production Proteome Rattus Regulation Rest Reticulum Rodent Sample Size Skeletal Muscle Small Interfering RNA Sodium Strenuous Exercise Structure Testing Tissues Tracer Variant Woman acipimox age effect cohort design flexibility glucose disposal human tissue male men model design negative affect oxidation oxidized lipid preservation protein expression respiratory response sedentary stoichiometry subcutaneous

项目摘要

Summary/Abstract Metabolic flexibility refers to the ability to switch between carbohydrate (CHO) and fat oxidation in response to changing physiological conditions. A mixed-model design is proposed to interrogate the hypothesis that the loss of metabolic flexibility in aging is of mitochondrial origin. The design calls for studies on intact humans, human skeletal muscle (SM) and white adipose tissue (WAT) as well as on rat and mouse SM and WAT. A segment of the effort on cells and organelles isolated from young and old lab rodents will be necessary to perform extensive respiratory control studies as well as studies of mitochondrial dynamics and composition, whereas because of sample size limitations, studies an human mitochondrial preparations will be involve selective analyses. To test the main hypothesis four cohorts of humans will be studied: sedentary (< 2 hr vigorous PA/wk) and physically active (>5 hr PA/wk) young healthy controls (21-35 yr), older sedentary and physically active individuals (60-80 yr) of age. Tissues will be harvested from analogous rat populations, 3-4 month (mo) and 21-23 mo old male and female F344 rats and young (2-3 mo) and old (15 mo) GPR81 null mice (Aim 4).

摘要/摘要代谢灵活性是指响应于碳水化合物（CHO）和脂肪氧化之间的能力改变生理状况。提出了一种混合模型设计，以审问损失的假设衰老的代谢柔韧性是线粒体起源的。设计要求研究完整人类，人类骨骼肌肉（SM）和白脂肪组织（WAT）以及大鼠和小鼠SM和WAT。一部分努力从小和老实验室啮齿动物中分离出的细胞和细胞器对于进行广泛的呼吸控制是必要的研究以及线粒体动力学和组成的研究，而由于样本量的限制，研究人类线粒体制剂将涉及选择性分析。测试主要假设四个队列将研究人类：久坐（<2 hr剧烈的pa/wk），身体活跃（> 5 hr pa/wk）年轻人健康对照（21 - 35年），年龄较大的久坐和身体活跃的个体（60 - 80岁）。组织将从类似的大鼠种群，3-4个月（MO）和21-23 Mo Old雄性和女性F344大鼠和年轻人（2-3 mo）和Old（15 MO）GPR81无效小鼠（AIM 4）。