Claude D. Pepper Older Americans Independence Center

描述（由申请人提供）：该修订版将OAIC的重点扩展到“线粒体功能和疲劳”。疲劳是老年人的主要抱怨，与失去独立性和损伤密切相关，无论潜在的医疗条件如何。多种生物和心理社会因素可能会导致或影响疲劳。特别是，骨骼肌线粒体功能障碍可导致能量产生减少，这可能导致疲劳。对线粒体功能和疲劳的新关注将补充和加强父母补助金的肌肉减少症主题。为了解决这个新的重点，我们建议修改三个OAIC核心，增加新的评估和一个新的试点研究。临床研究核心将包括评估全身能量效率和利用率（V02 peak）的耗氧量指标、线粒体功能的体内MRI评估、活动监测以及疲劳的综合健康和心理社会评估，以表征疲劳的表型。基因组学，代谢和生物标志物核心将提供以下新技术：（a）活体多光子激发激光扫描显微镜，以获得线粒体功能以及铁（Fe）积累和定位的评估，（B）高分辨率呼吸测定法，以评估线粒体呼吸以及电子传递链和原位OXPHOS能力，（c）蓝色非变性凝胶电泳（BN PAGE），以确定单个线粒体呼吸复合物的含量和酶活性，和（d）基于阵列的基因组分析，以鉴定与肌肉线粒体功能和铁（Fe）稳态相关的基因型和表型差异，利用全基因组关联研究和外显子表达分析。生物统计和数据管理核心将实施生物信息学和基因组数据分析。经济影响佛罗里达大学（UF）对当地和区域经济有很大贡献。在2008年，UF创造了2,525个工作岗位，最近的研究表明，UF每年为佛罗里达的经济贡献近60亿美元。该大学直接在其主校区雇用约34，000人，并通过用友组织，如食品和农业科学研究所，负责在全州范围内创造74，894个就业机会。不幸的是，由于目前的经济环境，截至2009年4月16日 *，用友需要削减1.2亿美元的预算。这一削减将提高当地的失业率，并将在许多周边县震动。目前的计划将创造或保留8个工作岗位。 公共卫生相关性：疲劳是老年人的常见症状，通常与功能限制、损伤和残疾有关。了解疲劳的生物学机制可能有助于设计新的方法来避免疲劳，提高老年人的生活质量和独立性。

DESCRIPTION (provided by applicant): This revision expands the focus of the OAIC to "mitochondrial function and fatigue". Fatigue is a major complaint among older adults and is strongly associated with loss of independence and impairments regardless of underlying medical conditions. Multiple biological and psychosocial factors may contribute to or influence fatigue. In particular, skeletal muscle mitochondrial dysfunction can lead to reduced energy production, which could result in fatigue. The new focus on mitochondrial function and fatigue will complement and enhance the sarcopenia theme of the parent grant. To address this new focus we propose the revision of three OAIC cores with the addition of new assessments and a new pilot study. The Clinical Research Core will include oxygen consumption measures to assess whole body energy efficiency and utilization (V02peak), in vivo MRI assessments of mitochondrial function, activity monitoring, and comprehensive health and psychosocial assessments of fatigue to characterize the phenotype of fatigue. The Genomics, Metabolism and Biomarkers Core will provide the following novel technologies: (a) intravital multiphoton excitation laser-scanning microscopy to obtain assessments of mitochondrial function, and iron (Fe) accumulation and localization, (b) high-resolution respirometry to assess mitochondrial respiration, and electron transport chain and OXPHOS capacity in situ, (c) Blue native gel electrophoresis (BN PAGE) to determine content and enzymatic activity of the individual mitochondrial respiratory complexes, and (d) array-based genomic analysis to identify genotypic and phenotypic differences correlated with muscle mitochondrial function and iron (Fe) homeostasis, utilizing genome-wide association studies and exon expression analysis. The Biostatistics and Data Management Core will implement bioinformatics and analyses of genomic data. Economic impact The University of Florida (UF) contributes substantially to the local and regional economy. In 2008, UF created 2,525 jobs and recent studies have shown that UF contributes nearly $6 billion annually to Florida's economy. The university employs about 34,000 people directly on its main campus and via UF organizations, such as the Institute of Food and Agricultural Sciences, is responsible for the creation of 74,894 jobs statewide. Unfortunately, because of the current economic environment, as of April 16*, 2009 UF is required to cut $120 million from its budget. This cut will raise local unemployment rates and will vibrate across many surrounding counties. The current proposal will create or retain 8 jobs. PUBLIC HEALTH RELEVANCE: Fatigue is a common symptom in older populations and is often associated with functional limitations, impairments and disability. Understanding the biological mechanisms underlying fatigue may help to devise novel approaches to avert fatigue and improve quality of life and independence of older adults.