Aging: Effects on Infection, Inflammation and Disease

衰老：对感染、炎症和疾病的影响

基本信息

批准号：
6942672
负责人：
Michael John Novak
金额：
$ 23.32万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-01 至 2007-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This proposal is a collaborative submission from the University of Kentucky, the University of Maryland, and the Nutritional and Molecular Physiology Unit of the Laboratory of Neurosciences of the National Institute on Aging. The proposed studies will build on existing data obtained from Rhesus monkeys being maintained on calorie restricted and normal diets by the NIA, and will provide a biologic basis for our preliminary observations of altered inflammatory responses in calorie restricted animals. This proposal focuses on utilizing the oral cavity as a model system to examine the impact of aging on host-bacterial interactions as they relate to microbial colonization of mucosal surfaces, the induction and regulation of inflammatory/immune responses, and the pathologic destruction of host tissues that may result from these interactions. The aims of this study will test the following contrasting scientific hypotheses: (a) that caloric restriction (CR) reduces clinical inflammation by affecting the pathogenicity of microbial plaque, and that these changes are due to shifts in the proportions and/or clonal type of the constituent pathogenic and non-pathogenic microorganisms; (b) that CR alters the clinical manifestation of inflammation through an effect on innate immune mechanisms through increased pro-inflammatory molecule release; and/or (c) that CR alters the clinical manifestation of inflammation through an effect on innate immune mechanisms by regulating the release of anti-inflammatory molecules. Aim 1 is a cross-sectional retrospective study to determine the effects of a long-term calorie restricted diet on the progression of naturally occurring inflammatory periodontal disease in CR and non-CR Rhesus monkeys. The effects of CR on clinical inflammation, microbial colonization of mucosal surfaces, and pro-inflammatory and anti-inflammatory mechanisms will be evaluated. Aim 2 is a longitudinal prospective study to determine the effects of a calorie-restricted diet on the clinical, microbiological, and host responses observed during experimental ligature-induced periodontitis in the same CR and non-CR Rhesus monkeys. These studies will provide information on the effects of CR on the kinetics of clinical, microbiologic, and inflammatory changes at mucosal sites. The significance of these studies lies in our capability to use nonhuman primates and the oral cavity to evaluate the efficacy of CR as a means to regulate infection, inflammation, and inflammatory disease. The long-term implications are that diet control may be considered as an effective public healthcare measure for improving the oral and general health and welfare of the population as a whole.

描述（由申请人提供）：该提案是肯塔基大学，马里兰州大学以及美国国家衰老研究所神经科学实验室的营养和分子生理部门的合作提交。拟议的研究将基于NIA维持对卡路里限制和正常饮食的恒河猴获得的现有数据，并将为我们对卡路里受限动物的炎症反应改变的初步观察提供生物学基础。该提案的重点是利用口腔作为模型系统，以检查衰老对宿主 - 细菌相互作用的影响，因为它们与粘膜表面的微生物定殖，炎症/免疫反应的诱导和调节以及可能由这些相互作用导致的宿主组织的病理破坏。这项研究的目的将测试以下对比的科学假设：（a）热量限制（CR）通过影响微生物斑块的致病性来减少临床炎症，并且这些变化是由于比例的变化和/或克隆类型的变化所致，是组成型的致病性和非疾病和非疾病生态学的微型生殖器良好性的。（b）通过增加促炎性分子释放对先天免疫机制的影响来改变炎症的临床表现；和/或（c）通过调节抗炎分子的释放，通过对先天免疫机制的影响来改变炎症的临床表现。 AIM 1是一项横断面回顾性研究，旨在确定长期卡路里饮食对CR和非CR恒河猴自然炎症牙周疾病的发展的影响。将评估CR对临床炎症，粘膜表面微生物定植以及促炎和抗炎机制的影响。 AIM 2是一项纵向前瞻性研究，旨在确定限制卡路里的饮食对在同一CR和非CR恒河猴实验性结扎诱导的牙周炎期间观察到的临床，微生物和宿主反应的影响。这些研究将提供有关CR对粘膜部位临床，微生物和炎症变化动力学的影响的信息。这些研究的重要性在于我们使用非人类灵长类动物和口腔来评估CR作为调节感染，炎症和炎症性疾病的手段的能力。长期的影响是，可以将饮食控制视为改善整个人口的口腔和一般健康和福利的有效公共医疗措施。