Dissecting connections between age, health and Alzheimer's disease

剖析年龄、健康与阿尔茨海默病之间的联系

基本信息

批准号：
10263907
负责人：
HEIDI A TISSENBAUM
金额：
$ 20.94万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10263907
关键词：
Address Affect Age Age-associated memory impairment Aging Agreement Alzheimer&apos s Disease Alzheimer&apos s disease model Amyloid Amyloid beta-Protein Animals Biological Assay Biological Models Caenorhabditis elegans Complex Disease Funding Geroscience Health Health Care Costs Heat Stress Disorders Human IGF-1 Signaling Pathway Individual Insulin Insulin-Like Growth Factor I Kinetics Liquid substance Longevity Mammals Mitochondria Modeling Molecular Molecular Genetics Movement Muscle Muscle function Neurodegenerative Disorders Onset of illness Oxidative Stress Parental Ages Population Process Publishing Recombinants Resistance Risk Factors Severities Signal Pathway Signal Transduction Signaling Protein Solid System Testing Transgenic Animals Transgenic Organisms Translations Ursidae Family age effect age related aged biological adaptation to stress dietary restriction frailty healthspan healthy aging illness length muscular structure mutant stem tool

项目摘要

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.

抽象的随着我们人口的年龄，与年龄相关的个体人数有所增加包括阿尔茨海默氏病在内的疾病，导致巨大的社会烧伤，爆炸性医疗保健成本增加。目前，在美国，超过500万人受到阿尔茨海默氏病，无法治愈。该建议旨在填补我们对老化过程与发作和严重程度之间的基本机械联系阿尔茨海默氏病。该提案的基础源于我们成功发表的健康衰老我们现在将应用于阿尔茨海默氏症的转基因动物的模型直接测试年龄和荒地动物会影响阿尔茨海默氏病。我们使用秀丽隐杆线虫作为我们的系统，因为秀丽隐杆线虫有一个短（在20°C下为2-3周）和不变寿命。此外，秀丽隐杆线虫保存良好胰岛素/IGF-1信号传导途径，几种与人类类似的年龄相关变化；配置的信号途径；并具有带有重组人淀粉样动物的阿尔茨海默氏病转基因动物 Aβ。在AIM 1中，我们将解决变化的衰老和健康动力学如何定义发作和/或人Aβ转基因动物的严重程度。在AIM 2中，我们将剖析年龄对人Aβ的影响转基因动物。总体而言，我们将检验Geroscience假设，即诸如阿尔茨海默氏症之类的疾病是衰老过程。由于我们的评估测试了广泛的功能，因此我们也被中毒，以更好地了解衰老过程与阿尔茨海默氏症之间的关系疾病。