ROLE OF IL-1 ADAPTATION IN AGING MUSCLE

IL-1 适应在肌肉老化中的作用

• 批准号: 7377663
• 负责人: CHARLOTTE A. PETERSON
• 金额: $ 0.39万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377663
• 关键词: ROLE; IL; ADAPTATION; AGING; MUSCLE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Interleukin-1 (IL-1) and the inflammatory response are important for initiating structural and functional repair of muscle after damaging exercise. However, this inflammatory response must be regulated to prevent further muscle damage. We hypothesize that with aging this regulatory mechanism may fail so that muscle wasting occurs. On the other hand, inability to mount an effective inflammatory-regenerative response in some older individuals may compromise muscle adaptation to exercise. Given that the IL-1 genotype appears to influence diverse physiologic processes, we propose to determine whether there is a correlation among the muscle inflammatory response after an acute bout of resistance exercise, IL-1 abundance, and IL-1 genotype in the elderly. We hypothesize that IL-1 polymorphisms modulate muscle responses to damage and that IL-1 expression and the inflammatory response after an acute exercise bout are predictive of the adaptability of muscle of elderly individuals to chronic resistance training. We will determine whether differences in IL-1 activity contribute to the variability of muscle adaptation to exercise, particularly evident in the elderly, and may even contribute to the "failure to thrive" phenotype that jeopardizes functional independence in the elderly. Specific Aim 1. Determine whether there is a correlation between the muscle inflammatory response after an acute bout of resistance exercise and IL-1 abundance at the mRNA and protein levels, and if these differ across different IL-1 genotypes in the elderly. For genotyping, the five single-nucleotide polymorphisms shown to be associated with variations in IL-1 abundance or diverse biologic functions will be examined; these include IL-1A (-889), IL-1A (+4845), IL-1B (+3954), IL-1B (-511), and IL-1RN (+2018). Specific Aim 2. Determine whether IL-1 expression and the inflammatory response after an acute exercise bout are predictive of the hypertrophic response of muscle of elderly individuals to chronic resistance training. The work of this aim will involve a subset of the individuals studied in Aim 1 with the widest range of responses. Muscle fiber size and muscle mass will be quantitated, as well as the accumulation of gene products common to AD and inclusion-body myositis (IBM), including IL-1, IL-1 converting enzyme (ICE), bAPP, amyloid-b (Ab), tumor necrosis factor-a (TNF-a), and hyperphosphorylated tau. This analysis will be combined with gene expression profiling using cDNA microarrays to determine whether different IL-1 gene expression levels are associated with specific phenotypes in exercised muscle that may predict adaptability to exercise. The goal of this project is to identify underlying molecular mechanisms that prevent muscle adaptation to exercise and potentially contribute to muscle wasting during aging. Given the pivotal role of IL-1 in the recovery of muscle from damage and the association of IL-1 polymorphisms with a variety of immune-mediated diseases, IL-1 is a strong candidate for playing a major role in the variability in muscle response to exercise with age.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。白介素-1（IL-1）和炎症反应对于在损害运动后启动肌肉的结构和功能修复很重要。但是，必须调节这种炎症反应以防止进一步的肌肉损害。我们假设随着年龄的增长，这种调节机制可能会失败，以便发生肌肉浪费。另一方面，某些年龄较大的人无法在某些年龄较大的人中进行有效的炎症再生反应，这可能会损害运动的肌肉适应性。鉴于IL-1基因型似乎会影响多样化的生理过程，我们建议确定在抗药性运动，IL-1丰度和IL-1基因型中，肌肉炎症反应之间是否存在相关性。我们假设IL-1多态性调节肌肉对损伤的反应，并且急性运动后IL-1表达和炎症反应可预测老年人对慢性抵抗训练的肌肉的适应性。我们将确定IL-1活性的差异是否有助于肌肉适应运动的变异性，尤其是在老年人中显而易见，甚至可能有助于“不蓬勃发展”表型，从而危及老年人的功能独立性。 具体目的1。确定在抗药性运动急性反应和在mRNA和蛋白质水平下的IL-1丰度后的肌肉炎症反应之间是否存在相关性，以及老年人在不同的IL-1基因型之间是否有所不同。对于基因分型，将检查与IL-1丰度或多种生物学功能的变化有关的五个单核苷酸多态性。其中包括IL-1A（-889），IL-1A（+4845），IL-1B（+3954），IL-1B（-511）和IL-1RN（+2018）。具体目的2。确定急性运动后IL-1表达和炎症反应是否可以预测老年人对慢性抵抗训练的肌肉的肥大反应。该目标的工作将涉及在AIM 1中研究的一个子集，其响应范围最广​​。肌肉纤维的大小和肌肉质量将被定量，以及AD和纳入体肌炎（IBM）共同的基因产物的积累，包括IL-1，IL-1转化酶（ICE），BAPP，淀粉样蛋白B（ AB），肿瘤坏死因子A（TNF-A）和高磷酸化的TAU。该分析将与使用cDNA微阵列结合基因表达分析，以确定不同的IL-1基因表达水平是否与运动肌肉中的特定表型相关，以预测可能适应运动的适应性。该项目的目的是识别潜在的分子机制，以防止肌肉适应运动，并可能导致衰老期间肌肉浪费。鉴于IL-1在从损害中恢复肌肉以及IL-1多态性与各种免疫介导的疾病中的关联中的关键作用，IL-1是在肌肉反应中发挥重要作用的有力候选者随着年龄的增长。