Dissecting connections between age, health and Alzheimer's disease

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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.