Dissecting connections between age, health and Alzheimer's disease

摘要 随着我们的人口老龄化，与年龄相关的个人数量急剧增加 包括阿尔茨海默病在内的疾病， 增加医疗保健费用。目前，在美国，超过500万人受到 老年痴呆症，而且没有治愈的方法。这项建议旨在填补我们对以下问题的理解上的差距： 衰老过程与衰老的发生和严重程度之间的潜在机械联系 老年痴呆症这一建议的基础源于我们成功发表的健康老龄化 我们现在将应用于阿尔茨海默氏症转基因动物的模型，以直接测试年龄和健康状况如何 会影响老年痴呆症我们使用C。elegans作为我们的系统，因为C.优雅的人有一个 寿命短（20°C时2-3周）且不变。此外，C.秀丽线虫有一个保守的 胰岛素/IGF-1信号通路，几种与人类相似的年龄相关变化;保守信号通路 途径;并具有携带重组人淀粉样蛋白的阿尔茨海默病转基因动物 Aβ。在目标1中，我们将讨论如何改变衰老和健康动力学定义的发病和/或 人Aβ转基因动物的严重程度。在目标2中，我们将分析年龄对人类Aβ的影响， 转基因动物总的来说，我们将测试老年科学假设，即一个主要的风险因素， 老年痴呆症等疾病是衰老的过程。由于我们的分析测试了广泛的功能， 我们还准备更好地了解衰老过程和阿尔茨海默氏症之间的关系， 疾病

Abstract As our population ages, there is a steep rise in the number of individuals with age associated illness including Alzheimer's disease resulting in a tremendous societal burden with explosive increases in health care costs. Currently, in the USA, over five million people are affected by Alzheimer's Disease and there is no cure. This proposal aims to fill the gap in our understanding of the underlying mechanistic connections between the aging process and the onset and severity of Alzheimer's Disease. The basis of this proposal stems from our successfully published healthy aging model that we will now apply to Alzheimer's transgenic animals to directly test how the age and heath of an animal affects Alzheimer's disease. We use C. elegans as our system since C. elegans have a short (2-3 weeks at 20°C) and invariant lifespan. In addition, C. elegans have a well-conserved insulin/IGF-1 signaling pathway, several age-related changes similar to humans; conserved signaling pathways; and have Alzheimer’s disease transgenic animals which bear recombinant human amyloid Aβ. In Aim 1, we will address how changing aging and health kinetics defines the onset and/or severity of a human Aβ transgenic animal. In Aim 2, we will dissect the effect of age on a human Aβ transgenic animal. Overall, we will test the Geroscience hypothesis that a major risk factor for a disease such as Alzheimer's is the aging process. Since our assays test a broad array of functions, we are also poised to better understand the relationship between the aging process and Alzheimer’s disease.