Genetics of Aging and Innate Immunity in Drosophilla

果蝇衰老和先天免疫的遗传学

• 批准号: 6940655
• 负责人: SCOTT PLETCHER
• 金额: $ 7.53万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6940655
• 关键词: Drosophilidae; Escherichia coli; aging; animal mortality; bacterial disease; bactericidal immunity; immune response; immunofluorescence technique; immunogenetics; immunosenescence; physiology; tissue /cell culture

DESCRIPTION (provided by applicant): Immunosenescence is the age-dependent deterioration of immune function that contributes to increased susceptibility of the elderly to infection. It is a hallmark of aging and is known to contribute to age-dependent increases in mortality, morbidity, and potentially cancer. The mammalian immune response consists of two components: an adaptive (also called acquired) response and an innate response. Innate immunity involves such things as recognition of microorganisms, secretion of anti-microbial peptides, and recruitment of the adaptive response. Aspects of both the adaptive and innate response are subject to deterioration with advancing age. Mechanisms of innate immunity are highly conserved across species, and the success of Drosophila as a model system in both the genetics of innate immunity and the genetics of aging make it an ideal candidate for investigating the interaction between these two processes. There are indications that innate immunity and aging are closely linked in this species. Dramatic increases in transcript representation with age have been observed for several key immune-regulated genes, and some, but not all, of these increases were linked to the rate of aging because they were ameliorated in long-lived flies. The primary goals of this application are to extend the intriguing observations described above and to systematically investigate immune function in the context of physiological changes that accompany normal aging in Drosophila. This work will provide the first description of the impact of aging on fly immunity, will establish preliminary data for future funding applications concerning the genetics of immunosenescence, and will test the viability of Drosophila as a model system for this type of research. We will test the hypothesis that the innate immune response is a causative factor in determining aging-related mortality. We will also measure the physiological and transcriptional response to controlled exposure to infectious agents and determine whether lifespan in Drosophila is limited by natural exposure to pathogens.

描述（由申请人提供）：免疫衰老是免疫功能的年龄依赖性恶化，这有助于增加老年人对感染的敏感性。它是衰老的标志，已知会导致死亡率，发病率和潜在癌症的年龄依赖性增加。哺乳动物免疫反应由两个组成部分组成：一种适应性（也称为获得的）反应和先天反应。先天免疫涉及对微生物的识别，抗菌肽的分泌以及适应性反应的招募。适应性和先天反应的各个方面都会随着年龄的增长而恶化。 先天免疫的机制在整个物种之间都是高度保守的，果蝇作为模型系统在先天免疫的遗传学和衰老的遗传学中的成功使其成为研究这两个过程之间相互作用的理想候选者。有迹象表明，在该物种中，先天免疫和衰老与这种物种紧密相关。对于几个关键的免疫调节基因，已经观察到了随着年龄的增长的急剧增加，其中一些（但不是全部）与衰老率有关，因为它们在长寿命中得到了改善。 本应用的主要目标是扩展上述有趣的观察结果，并在果蝇正常衰老的生理变化的背景下系统地研究免疫功能。这项工作将提供对衰老对苍蝇免疫力的影响的首先描述，将为有关免疫衰老遗传学的未来资金应用建立初步数据，并将测试果蝇作为此类研究的模型系统的可行性。 我们将检验以下假设：先天免疫反应是确定与衰老相关的死亡率的原因。我们还将测量对感染剂的受控暴露的生理和转录反应，并确定果蝇中的寿命是否受到病原体的自然暴露限制。