Mechanisms of reduced regenerative potential in aging skeletal muscle

衰老骨骼肌再生潜力降低的机制

基本信息

批准号：
8443387
负责人：
Leonardo Ferreira
金额：
$ 6.92万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8443387
关键词：
Activities of Daily Living Acute Address Adult Age Aging Amaze Animal Model Animals Antioxidants Antisense Oligonucleotides Arginine Basic Science Binding Cell Culture Techniques Cell Differentiation process Cells Coupled Data Development Diet Elderly Environment Event Failure Fatigue Genetic Growth Healthcare Human Hypertrophy Immune Impairment Infiltration Inflammation Inflammation Mediators Inflammatory Inflammatory Response Injury Knockout Mice Life Location Maintenance Mechanics Metabolic Control Metabolic Diseases Methods Modeling Molecular Mouse Strains Movement Mus Muscle Muscle Fibers Muscle rehabilitation Muscle satellite cell NF-kappa B NG-Nitroarginine Methyl Ester Natural regeneration Nitric Oxide Nitric Oxide Synthase Type I Oxidation-Reduction Oxidative Stress Performance Perfusion Phase Procedures Process Production Proteins Recovery Rehabilitation therapy Risk Rodent Signal Transduction Skeletal Muscle Skeletal muscle injury Staging Stress Supplementation TRIM Gene Testing Therapeutic Effect Time Translating Translations aged angiogenesis arginine treatment design dietary antioxidant dietary supplements experience frailty improved in vivo injured knock-down muscle form muscle regeneration muscle strength novel prevent protein expression regenerative research study restricted physical activity sarcopenia satellite cell tibialis anterior muscle tissue repair treatment strategy young adult

项目摘要

DESCRIPTION (provided by applicant): As we age, the regenerative capacity of skeletal muscle declines, prolonging or preventing complete recovery and rehabilitation from muscle injury. In fact older adults often never recover muscle mass and strength following an injury; leading to fatigue, activity limitations, and ultimately a loss of independence. Background: Effective recovery of injured skeletal muscle is driven by activation of resident satellite cells. Concurrently, the inflammatory response clears cellular debris and promotes satellite cell differentiation. However, the inflammatory process can also delay recovery by damaging cellular components via oxidative stress. Satellite cells retain their regenerative potential throughout lif, if exposed to the proper environment. Therefore, dietary supplements designed to augment satellite cell activity and minimize oxidative stress have the potential to improve skeletal muscle rehabilitation following acute injury. Hypotheses and Approach: L-arginine can act as an antioxidant, as well as a stimulator of satellite cell activation in cell culture. Therefore, we propose a novel application of dietary L-arginine therapy to simultaneously augment satellite cell activity and inhibit inflammatory stress in vivo. This project will translate our preliminary cell culture data into an in vivo animal model and explore the mechanisms underlying the functional effects of L- arginine in adult skeletal muscle. We hypothesize that L-arginine supplementation following acute myotoxin injury will augment recovery of muscle mass by inhibiting activation of the inflammatory mediator, NF-kB, and enhancing activation of resident satellite cells. Further, that these effects will be dependent upon nitric oxide production. Significance: Physical rehabilitation following muscular injury is a major health care expense. More importantly, the loss of muscle mass with aging coupled with the failure to fully recover muscle following injury leads to physical frailty and increased risk of metabolic disease. Therefore, this project seeks to improve our mechanistic understanding of muscle regeneration and translate basic science data into effective dietary supplement strategies to augment muscle injury recovery. and contractile function in aging mice

描述（由申请人提供）：随着年龄的增长，骨骼肌的再生能力下降，延长或防止肌肉损伤完全恢复和康复。实际上，老年人受伤后通常永远不会恢复肌肉质量和力量。导致疲劳，活动限制，最终导致独立性丧失。背景：有效恢复受伤的骨骼肌是由居民卫星细胞激活驱动的。同时，炎症反应清除细胞碎屑并促进卫星细胞分化。但是，炎症过程还可以通过氧化应激损害细胞成分来延迟恢复。如果暴露于适当的环境，卫星细胞将在整个LIF中保持其再生潜力。因此，旨在增强卫星细胞活性并最大程度减少氧化应激的饮食补充剂具有改善骨骼肌肉的潜力急性受伤后的康复。假设和方法：L-精氨酸可以充当抗氧化剂，以及细胞培养中卫星细胞激活的刺激剂。因此，我们提出了饮食中L-精氨酸疗法的新型应用，以同时增强卫星细胞活性并抑制体内炎症胁迫。该项目将我们的初步细胞培养数据转化为体内动物模型，并探索L-精氨酸在成人骨骼肌中功能效应的基础机制。我们假设急性肌毒素损伤后的L-精氨酸补充将通过抑制炎症介质的激活，NF-KB的激活来增加肌肉质量的恢复，并增强居民卫星细胞的激活。此外，这些作用将取决于一氧化氮的产生。意义：肌肉损伤后的身体康复是主要的医疗保健费用。更重要的是，随着衰老的衰老，肌肉质量的损失以及受伤后无法完全恢复肌肉的损失会导致身体脆弱和代谢疾病的风险增加。因此，这个项目试图提高我们对肌肉再生的机械理解，并将基础科学数据转化为有效的饮食补充策略，以增加肌肉损伤的恢复。和老化小鼠的收缩功能