Maximizing Mechanisms of Muscle Hypertrophy to Combat Sarcopenia in Older Adults

最大化肌肉肥大的机制来对抗老年人的肌肉减少症

基本信息

批准号：
7583959
负责人：
MARCAS M BAMMAN
金额：
$ 32.82万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7583959
关键词：
70-kDa Ribosomal Protein S6 Kinases Actins Acute Adult Affect Age Atrophic Automobile Driving Binding Proteins Cell Cycle Cell Cycle Regulation Cell Differentiation process Cell Nucleus Communities Comorbidity Contractile Proteins Cyclin D1 Data Dose Elderly Environment Enzymes Epidemic Eukaryotic Initiation Factors Evaluation Event Exercise Fatigue Fiber Funding Gender Genetic Transcription Growth Housing Hypertrophy Immunoblotting Inferior Infusion Technique Insulin-Like Growth Factor Binding Protein 4 Insulin-Like Growth Factor I Intervention Laboratories Lead Low income Measurable Measures Mechanics Mediating Messenger RNA Metabolic Methods Modeling Molecular Motor Muscle Muscle Proteins Muscle function Muscular Atrophy Myf-6 myogenic factor Myogenin Myosin Heavy Chains Natural regeneration Nuclear Outcome Participant Pathway interactions Performance Phosphorylation Plant Roots Population Process Production Protein Biosynthesis Proteins Public Health Quality of life RNA Splicing Randomized Recovery Relative (related person)Research Research Project Grants Resistance Rest Reverse Transcriptase Polymerase Chain Reaction Series Sex Characteristics Signal Transduction Skeletal Muscle Specificity Stem cells Stress Techniques Testing Time Training Training Programs Translating Translation Initiation Treatment Protocols Ubiquitin Ubiquitin-Activating Enzymes Up-Regulation Variant Walking Weight-Bearing state Woman Work age related base caspase-3 combat design effective therapy human FRAP1 protein improved improved mobility in vivo indexing innovation loss of function men multicatalytic endopeptidase complex muscle form muscle hypertrophy myostatin novel older women performance tests programs protein activation protein degradation regenerative response sarcopenia satellite cell stable isotope strength training transcription factor ubiquitin-protein ligase

项目摘要

DESCRIPTION (provided by applicant): Age-related skeletal muscle atrophy (i.e., sarcopenia) accelerates beyond the fifth decade and leads to functional limitations and comorbidities that markedly impair quality of life. Resistance training has shown the most promise among treatments to combat sarcopenia as it enhances muscle function, but induces varying degrees of muscle hypertrophy. The overarching aim is to build on current work in older (60-75 yr) vs. young (20-35 yr) women and men by advancing the understanding of resistance training adaptations using a dose-response approach in older adults, ultimately leading to optimal training program design to combat sarcopenia. A novel resistance training model will be explored (versus 3 others) that is predicted to surpass previous attempts to improve key losses of function associated with sarcopenia (strength, power, and fatigue resistance) by maximizing its impact on the root sarcopenia itself (i.e. by increasing muscle mass and integrity). Myofiber hypertrophy requires net muscle protein synthesis and, as demonstrated during the current funding period/advanced fiber expansion is facilitated by nuclear addition. Over the past 4.25 years of support, key cellular/molecular events within skeletal muscle that likely drive these processes have been identified, and several have been shown to respond in an age- and gender-dependent manner to resistance exercise. Four 30-wk resistance training models will be tested in 60-75 yr adults (n=88: 22 per model; 11 women, 11 men) after 4 wk of pre-training to determine which model maximizes muscle growth/regeneration. There are three specific aims: 1) to evaluate the gender-specific efficacy of each model based on muscle hypertrophy and performance; 2) to assess net muscle protein synthesis and myonuclear addition, along with key cellular/molecular myogenic processes, driving differences in growth among the models in a potentially gender-specific manner; and 3) to translate the findings of aim 1 to clinically important outcomes by determining the degree to which non-traditional training programs improve mobility function. Relevance: As the U.S. population 65+ yr of age expands to 70 million by 2030, sarcopenia will become a large-scale public health issue as the number of older adults suffering functional limitations will reach epidemic proportions in the absence of effective treatments. The proposed research is a critical step toward defining a broadly applicable intervention to maximize gains in muscle mass and function among elderly.

描述（由申请人提供）：与年龄相关的骨骼肌萎缩（即肌肉减少症）可加速第五个十年，并导致功能局限性和合并症显着损害了生活质量。耐药训练在治疗中表现出最大的前景来对抗肌肉减少症，因为它可以增强肌肉功能，但诱导了不同程度的肌肉肥大。总体目的是基于在老年人中使用剂量反应方法来促进对抵抗运动训练适应的理解，最终导致最佳的培训计划设计，以促进对抗肌肉折磨的最佳训练计划设计，以促进对抵抗训练适应的理解，以促进对抵抗训练适应的理解，从而建立在年龄较大（60 - 75年）与年轻人（20 - 35年）中的当前工作。将探索一种新型的阻力训练模型（与其他3个），预计将超过以前的尝试，以改善与肌肉减少症相关的关键功能损失（强度，力量，功率和疲劳性抗性），通过最大程度地提高其对根部萨科尼亚本身的影响（即通过提高肌肉质量和完整性）。肌纤维肥大需要净肌肉蛋白质合成，正如当前资金期间/晚期纤维扩张所证明的那样，核添加促进了。在过去的4。25年的支持中，骨骼肌内可能驱动这些过程的关键细胞/分子事件已被鉴定出来，并且已证明有几个可以以年龄和性别依赖性方式响应抵抗运动。在60 - 75年的成年人中，将测试四个30周的耐药性训练模型（每次模型n = 88：22； 11名女性，11名男性），以确定哪种模型最大化肌肉生长/再生。有三个特定的目的：1）根据肌肉肥大和表现评估每个模型的性别特异性功效； 2）评估净肌肉蛋白的合成和肌核添加，以及关键的细胞/分子肌源过程，以潜在的性别特异性方式推动模型之间的生长差异； 3）通过确定非传统培训计划改善移动性功能的程度，将目标1的发现转化为临床上重要的结果。相关性：随着美国65岁以上年龄的人口到2030年的7000万年龄，肌肉减少症将成为一个大规模的公共卫生问题，因为在没有有效治疗的情况下，遭受功能限制的老年人的数量将达到流行比例。拟议的研究是定义广泛适用的干预措施以最大程度地提高肌肉质量和老年人功能的关键步骤。