Skeletal Muscle lipid and Insulin Resistance in Aging

衰老过程中的骨骼肌脂质和胰岛素抵抗

基本信息

批准号：
8526303
负责人：
Bret H Goodpaster
金额：
$ 61.54万
依托单位：
ADVENTHEALTH ORLANDO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-15 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8526303
关键词：
1,2-diacylglycerol Acyl Coenzyme A Adult Aging Animal Model Atrophic Autophagocytosis Biochemical Biogenesis Biological Biopsy Specimen Body Weight decreased Ceramides Complex Development Diet Diglycerides Disease Energy Metabolism Evidence based intervention Exercise Functional disorder Growth Health High Prevalence Human Hydrogen Peroxide Insulin Resistance Intervention Lead Link Lipids Maintenance Mediating Metabolic Methods Mitochondria Moderate Exercise Molecular Molecular Profiling Molecular Target Muscle Muscle Proteins Muscle Weakness Muscle function Muscular Atrophy Non-Insulin-Dependent Diabetes Mellitus Obesity Overweight Oxidation-Reduction Oxidative Stress Pathway interactions Performance Physical activity Play Prevention strategy Randomized Controlled Trials Role Signal Transduction Skeletal Muscle Sphingolipids Therapeutic Training Triglycerides Weight Woman age related base clinically relevant cost disability improved innovation insulin sensitivity intervention effect men muscle aging muscle form muscle strength novel older men older women prevent programs protein expression sarcopenia transcription factor treatment strategy

项目摘要

Aging is associated with alterations in skeletal muscle energy metabolism, insulin resistance and a higher prevalence of type 2 diabetes mellitus (T2DM). Aging is also associated with a progressive loss of muscle mass and increased adiposity, known as sarcopenic obesity, which leads to mobility limitations and disability. However, the causes of insulin resistance and sarcopenia in humans are not known. This project will provide novel information regarding potential factors underlying both metabolic dysfunction and sarcopenia in aging muscle - namely, mitochondria and the accumulation of intramyocellular lipids. Within this conceptual framework we will help elucidate the biological underpinnings of these two significant health problems related to aging. In addition, we will provide intervention-based evidence to better understand these complex age-related disorders and whether mitochondria or intramyocellular lipids are modifiable targets for improved prevention or treatment strategies for metabolic and muscle dysfunction. Therefore, our overall objectives are to employ highly innovative methods in muscle biopsy specimens in order to determine the functional and clinically relevant consequences of these interventions as well as alterations in several novel biochemical and molecular factors potentially underlying these intervention effects on human skeletal muscle.

衰老与骨骼肌能量代谢，胰岛素的改变有关 2型糖尿病（T2DM）的抗药性和较高的患病率。衰老也是与肌肉质量的逐渐丧失和肥胖增加有关，称为肌肉减少肥胖，导致流动性限制和残疾。但是，人类胰岛素抵抗和肌肉减少症的原因尚不清楚。这个项目将提供有关两种代谢的潜在因素的新信息衰老肌肉的功能障碍和肌肉减少症 - 即线粒体和细胞内脂质的积累。在这个概念框架内，我们将帮助阐明这两个与衰老有关的重要健康问题。此外，我们将提供基于干预的证据更好地了解这些复杂的年龄相关疾病线粒体还是细胞内脂质是可修改的靶标以改进代谢和肌肉功能障碍的预防或治疗策略。因此，我们的总体目标是在肌肉中采用高度创新的方法活检标本以确定功能和临床相关的标本这些干预措施的后果以及几种新型生化的变化和分子因素可能潜在地对这些干预对人骨骼的影响肌肉。