Aging Mitochondrial Fragmentation and Metabolic Inflexibility

衰老线粒体碎片和代谢不灵活

• 批准号: 10548471
• 负责人: GEORGE Austin BROOKS
• 金额: $ 11.24万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10548471
• 关键词: Adipose tissue; Age; Aging; Award; Carbohydrates; Cells; Fatty acid glycerol esters; Female; Harvest; Human; Inbred F344 Rats; Individual; Knockout Mice; Metabolic; Mitochondria; Mus; Organelles; Parents; Physiological; Population; Preparation; Rattus; Rodent; Sample Size; Skeletal Muscle; Testing; Tissues; design; flexibility; male; model design; oxidation; respiratory; response; sedentary

Summary/Abstract – No Changes from Parent Award 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 cohortsof 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-与母公司奖励相比无变化 代谢灵活性是指在碳水化合物（CHO）和脂肪氧化之间转换的能力， 对变化的生理条件的反应。提出了一种混合模型设计来询问 这一假说认为，衰老过程中代谢灵活性的丧失是线粒体起源的。该设计要求研究 完整的人、人骨骼肌（SM）和白色脂肪组织（WAT）以及大鼠和小鼠SM 和WAT。从年轻和年老的实验室啮齿动物中分离出的细胞和细胞器的一部分工作将在 进行广泛的呼吸控制研究以及线粒体动力学研究所必需的， 然而，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。为了验证主要假设，将研究四组人：久坐不动的（< 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）， 和身体活跃的个体（60-80岁）。将从类似的大鼠群体中收获组织，3- 4-月龄（mo）和21- 2 - 3月龄雄性和雌性F344大鼠以及年轻（2-3月龄）和老年（15月龄）GPR 81无效 小鼠（Aim 4）。

项目成果

Underfeeding Alters Brain Tissue Synthesis Rate in a Rat Brain Injury Model.

• DOI: 10.3390/ijms241713195
• 发表时间: 2023-08-25
• 期刊: International journal of molecular sciences
• 影响因子: 5.6

The "Anaerobic Threshold" Concept Is Not Valid in Physiology and Medicine.

• DOI: 10.1249/mss.0000000000002549
• 发表时间: 2021-05-01
• 期刊: MEDICINE & SCIENCE IN SPORTS & EXERCISE
• 影响因子: 4.1
• 作者: Brooks, George A.

Lactate as a myokine and exerkine: drivers and signals of physiology and metabolism.

• DOI: 10.1152/japplphysiol.00497.2022
• 发表时间: 2023-03-01
• 期刊: JOURNAL OF APPLIED PHYSIOLOGY
• 影响因子: 3.3
• 作者: Brooks, George A.;Osmond, Adam D.;Arevalo, Jose A.;Duong, Justin J.;Curl, Casey C.;Moreno-Santillan, Diana D.;Leija, Robert G.
• 通讯作者: Leija, Robert G.

Fractional Gluconeogenesis: A Biomarker of Dietary Energy Adequacy in a Rat Brain Injury Model.

• DOI: 10.3390/metabo12121163
• 发表时间: 2022-11-23
• 期刊: Metabolites
• 影响因子: 4.1
• 作者: Curl CC;Kumar A;Peck AJ;Arevalo JA;Gleason A;Leija RG;Osmond AD;Duong JJ;Miller BF;Horning MA;Brooks GA
• 通讯作者: Brooks GA

Tracing the lactate shuttle to the mitochondrial reticulum.

追踪乳酸穿梭至线粒体网。

• DOI: 10.1038/s12276-022-00802-3
• 发表时间: 2022-09
• 期刊: EXPERIMENTAL AND MOLECULAR MEDICINE
• 影响因子: 12.8
• 作者: Brooks, George A.;Curl, Casey C.;Leija, Robert G.;Osmond, Adam D.;Duong, Justin J.;Arevalo, Jose A.
• 通讯作者: Arevalo, Jose A.