Aging Mitochondrial Fragmentation and Metabolic Inflexibility

摘要/摘要 代谢灵活性指的是响应于代谢的改变而在碳水化合物（CHO）和脂肪氧化之间切换的能力。 改变生理条件。提出了一种混合模型设计，以询问以下假设： 衰老中的代谢灵活性是线粒体起源的。该设计要求对完整的人体，人体骨骼， 肌肉（SM）和白色脂肪组织（WAT）以及大鼠和小鼠SM和WAT。一部分的努力， 从年轻和年老的实验室啮齿动物中分离的细胞和细胞器将是进行广泛的呼吸控制所必需的 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， 对人类线粒体制备物的研究将涉及选择性分析。为了检验主要假设， 将研究的人：久坐（< 2小时剧烈PA/周）和体力活动（>5小时PA/周）的年轻健康 对照组（21-35岁）、久坐不动和身体活跃的老年人（60-80岁）。组织将从 相似的大鼠群体，3-4月龄（mo）和21- 2 - 3月龄的雄性和雌性F344大鼠以及年轻（2-3月龄）和老年（15 mo）GPR 81缺失小鼠（Aim 4）。

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).