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The role of type 2 diabetes on skeletal muscle atrophy and recovery following bed rest in older adults

2 型糖尿病对老年人卧床休息后骨骼肌萎缩和恢复的作用

基本信息

批准号：
10412070
负责人：
Paul Martin Coen
金额：
$ 69.13万
依托单位：
ADVENTHEALTH ORLANDO
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：
2018-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10412070
关键词：
3-Dimensional Acute Age Aging Atrophic Bed rest Biochemical Bioenergetics Biology Biopsy Body mass index Calcium Cardiolipins Ceramides Clinical Complication Data Development Diabetes Mellitus Disuse Atrophy Elderly Etiology Exercise Goals Health Hospitalization Human Immobilization Impairment In Situ Injury Insulin Resistance Intervention Investigation Label Link Lipids Measurement Mitochondria Molecular Molecular Target Muscle Muscle function Muscular Atrophy Non-Insulin-Dependent Diabetes Mellitus Outcome Patients Phenotype Physical Function Physical activity Physiological Play Pre-Clinical Model Predisposition Protein Biosynthesis Proteomics Public Health Reactive Oxygen Species Recovery Respiration Role Shotguns Skeletal Muscle Sphingolipids Stimulus Testing Time clinically relevant evidence base experience improved in vivo innovation lipid metabolism lipidomics mitochondrial dysfunction muscle form muscle strength novel oxidation precision medicine prevent programs response sarcopenia skeletal muscle wasting therapeutically effective

项目摘要

PROJECT SUMMARY Loss of muscle mass during periods of disuse due to illness or hospitalization and poor recovery have serious health consequences for older adults. The mechanisms underlying the atrophy response to disuse and subsequent recovery in humans, however, are not known. We posit that poor mitochondrial energetics and altered muscle lipid metabolism contribute to greater disuse- induced muscle atrophy and poor recovery. In addition, we believe that older subjects with type 2 diabetes have reduced mitochondria capacity and excess muscle lipids, which exacerbates the deleterious effect of bed rest on muscle mass and impairs recovery. Mitochondria play a fundamental role in muscle health and impaired mitochondrial energetics and muscle lipids have been shown to contribute to human aging and type 2 diabetes. The role of mitochondrial energetics in human muscle atrophy and recovery is not known. In this project, we will test the hypothesis that altered mitochondrial energetics in muscle atrophy and recovery via cardiolipin remodeling, elevated reactive oxygen species (ROS) emission and accumulation of specific muscle sphingolipids blunt anabolic stimuli and contribute to muscle atrophy and poor recovery. The overall objective of this project is to decipher mechanisms by which mitochondrial energetics and muscle lipids underlie early muscle catabolic and anabolic responses to disuse and recovery. Studying older adults with type 2 diabetes and using an exercise recovery program will provide a physiological context and will allow us to delineate novel mechanisms. Through innovative time course studies and measurements in serial human muscle biopsies, we will place the etiology of muscle atrophy firmly in the context of mitochondrial biology and will contribute to a better precision medicine approach to prevent and treat disuse atrophy.

项目总结在因病或住院和恢复不佳的时期失去肌肉质量的情况很严重。对老年人的健康影响。停用和停用后萎缩反应的潜在机制然而，人类随后的恢复尚不清楚。我们假设，线粒体能量不足和肌肉脂肪代谢改变有助于更大程度的停用- 导致肌肉萎缩，恢复不佳。此外，我们认为患有2型糖尿病的老年患者减少线粒体的能力和过量的肌肉脂肪，这加剧了床的有害影响靠肌肉休息会影响恢复。线粒体在肌肉健康和受损的线粒体能量和肌脂中起着重要作用。已被证明与人类衰老和2型糖尿病有关。线粒体能量学在生物信息学中的作用人类肌肉萎缩和恢复尚不清楚。在这个项目中，我们将测试更改后的假设线粒体能量学在肌肉萎缩和恢复中的作用--通过心磷脂重塑、活性氧升高物种(ROS)释放和积累特定肌肉鞘脂钝化合成代谢刺激和会导致肌肉萎缩和恢复不佳。这个项目的总体目标是破译线粒体能量学和肌肉脂肪是早期肌肉分解代谢和合成代谢对停用和恢复的反应的基础。研究老年人对于2型糖尿病和使用运动恢复计划将提供一个生理背景，并将允许我们来描绘新的机制。通过创新的时间进程研究和连续人类的测量肌肉活检，我们将坚定地把肌肉萎缩的病因学放在线粒体生物学和将有助于一种更好的精准医学方法来预防和治疗废用萎缩。