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

• 批准号: 10359290
• 负责人: HEIDI A TISSENBAUM
• 金额: $ 2.62万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10359290
• 关键词: Address; Affect; Age; Age-associated memory impairment; Aging; Agreement; Alzheimer' s Disease; Alzheimer' 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

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.

摘要 随着人口老龄化，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导致炸药造成巨大的社会负担 医疗保健成本的增加。目前，在美国，有500多万人受到 阿尔茨海默氏症是一种无法治愈的疾病。这项建议旨在填补我们对 衰老过程与糖尿病的发病和严重程度之间的潜在机制联系 阿尔茨海默氏症。这一建议的基础源于我们成功出版的《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 会影响阿尔茨海默氏症。我们使用线虫作为我们的系统，因为线虫有一个 寿命短(在20°C时为2-3周)和恒定寿命。此外，线虫有一种保存良好的 胰岛素/IGF-1信号通路，几种与年龄相关的变化，与人类相似；保守信号 途径；并拥有携带重组人淀粉样蛋白的阿尔茨海默病转基因动物 一辆β。在目标1中，我们将讨论不断变化的衰老和健康动力学如何定义发病和/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 转基因动物。总体而言，我们将测试老年科学假说，即 阿尔茨海默氏症等疾病是衰老的过程。因为我们的分析测试了一系列的功能， 我们也准备好更好地了解衰老过程和阿尔茨海默氏症之间的关系 疾病。