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Skeletal Muscle Basis for Improved Exercise Endurance in RGS14 KO

RGS14 KO 中提高运动耐力的骨骼肌基础

基本信息

批准号：
9513046
负责人：
STEPHEN F VATNER
金额：
$ 50.08万
依托单位：
RBHS-NEW JERSEY MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9513046
关键词：
Age Aging Blood Circulation Blood Vessels Blood flow Brown Fat Cardiovascular system Cause of Death Diabetes Mellitus Disease Elderly Energy Metabolism Excision Exercise Exercise Tolerance GTP-Binding Protein Regulators GTP-Binding Proteins Grant Impairment Individual Knock-out Knockout Mice Life Style Limb structure Longevity MEKs Mediating Mitochondria Modeling Molecular Mus Muscle Muscle Fibers Myocardial Oxidative Stress Pathway interactions Patients Performance Peripheral Physiological Population Public Health Receptor Signaling Regulation Role Signal Pathway Signaling Protein Skeletal Muscle Therapeutic Tissues Translating Transplantation Vascular Endothelial Growth Factors Work angiogenesis beta-adrenergic receptor disability endurance exercise exercise capacity exercise training improved inhibitor/antagonist novel public health relevance receptor small molecule inhibitor

项目摘要

DESCRIPTION (provided by applicant): The current submission is a revised application for our grant on effects of exercise in the receptor of G protein signaling 14 (RGS14) knock out (KO) mouse. The RGS14 KO model, demonstrates enhanced exercise tolerance and energy utilization, resulting not only in longevity, but more significantly, healthful aging. The RGS14 KO reduces beta adrenergic receptor signaling, which might be consistent with longevity, but novel and unexpected as a mechanism for improved exercise, the focus of this application, since enhanced beta adrenergic receptor signaling has always been associated with improved exercise performance. The RGS14 KO model has the additional novel, salutary attribute of increased brown adipose tissue, which is known to increase energy utilization and protect against diabetes, but is not known to mediate enhanced exercise performance, which will be examined in this application. Another key feature of the RGS14 KO is its ability to increase angiogenesis, which would also enhance exercise performance, since limitation of blood flow to exercising muscle causes exercise to cease. The major focus of the current application is to examine the physiological and molecular mechanisms mediating the brown adipose tissue and angiogenesis induced enhanced exercise capacity in the RGS14 KO model. This is important because reduced exercise tolerance is central to all patients with cardiovascular and other diseases, impairing a healthy life style and aging, and conversely enhanced exercise protects against disease and extends longevity. The RGS14 KO also mimics the beneficial features of exercise training. Accordingly, developing an RGS14 inhibitor that can be given to patients would recapitulate the beneficial effects of exercise training without the burden placed on patients to undergo daily exercise. This last point is the focus of Aim C1 in this application.