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.

抽象的随着人口老龄化，与年龄相关的人数急剧增加包括阿尔茨海默病在内的疾病造成了爆炸性的巨大社会负担目前，在美国，超过 500 万人受到医疗保健费用增加的影响。阿尔茨海默病目前尚无治愈方法，该提案旨在填补我们对阿尔茨海默病的认识空白。衰老过程与衰老的发生和严重程度之间的潜在机制联系该提案的基础源于我们成功发表的《健康老龄化》。我们现在将模型应用于阿尔茨海默氏症转基因动物，以直接测试年龄和健康状况我们使用秀丽隐杆线虫作为我们的系统，因为秀丽隐杆线虫具有寿命短（20°C 下 2-3 周）且不变。此外，线虫的寿命保存良好。胰岛素/IGF-1信号通路，与人类相似的保守信号通路的一些与年龄相关的变化；以及携带重组人淀粉样蛋白的阿尔茨海默病转基因动物在目标 1 中，我们将讨论衰老和健康动力学的变化如何定义发病和/或。人类 Aβ 转基因动物的严重程度在目标 2 中，我们将剖析年龄对人类 Aβ 的影响。总的来说，我们将测试老年科学的假设，即一个主要的危险因素。阿尔茨海默氏症等疾病是衰老过程，因为我们的检测测试了广泛的功能，我们也准备好更好地了解衰老过程与阿尔茨海默病之间的关系疾病。