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Longevity assurance interventions, metabolic health and Alzheimer's Disease

长寿保证干预措施、代谢健康和阿尔茨海默病

基本信息

批准号：
9761415
负责人：
Liou Sun
金额：
$ 50.61万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9761415
关键词：
3xTg-AD mouse APP-PS1 Address Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease risk American Amyloid beta-Protein Animal Model Animals Behavioral Biological Models Biology of Aging Body Weight decreased Brain Chronology Cognitive aging Comb animal structure Dementia Dependence Development Diet Dietary Intervention Disease Disease Progression Disease model Effectiveness Elderly Electrophysiology (science)Exhibits Foundations Future Generations Genetic Gerontology Glucose Goals Health Health Care Costs Homeostasis Human Incidence Insulin Insulin Resistance Intervention Investigation Laron Syndrome Lead Learning Lipids Longevity Malignant Neoplasms Memory Metabolic Metabolic dysfunction Metabolic syndrome Metabolism Methionine Mitochondria Modeling Molecular Mus Mutant Strains Mice Mutation Nerve Degeneration Neurodegenerative Disorders Neurosciences Non-Insulin-Dependent Diabetes Mellitus Obesity Organism Outcome Pathologic Pathology Pathway interactions Pharmaceutical Preparations Pharmacology Phenotype Physiological Process Public Health Rattus Research Risk Factors Rodent Rodent Model Senile Plaques Signal Pathway Somatotropin Somatotropin-Releasing Hormone Testing Treatment Efficacy Work Yeasts abeta deposition age related aging brain anti aging baby boomer cost effective diabetes risk dietary restriction disease phenotype epidemiology study healthspan hormonal signals improved insulin sensitivity middle age model development mortality mutant nervous system disorder novel novel strategies pathological aging preclinical study prevent response symptom treatment synaptic function tau Proteins tau aggregation therapy development

项目摘要

The mechanisms responsible for the age dependence of the onset of neurodegeneration are unknown, which represents a fundamental problem both in neuroscience and biogerontology. Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by dementia, deposition of beta amyloid (Aβ) plaques, and neurofibrillary tau tangles. Despite progress in developing treatments for the symptomatic relief of AD, most drugs only exhibit marginal benefits and no cure currently exists. Epidemiological and preclinical studies provide strong evidence that metabolic derangements including obesity, metabolic syndrome and type 2 diabetes constitute major risk factors for age-related diseases including dementia and AD but the mechanisms involved remain to be elucidated. The GH signaling functions as a central regulator of metabolism and energy use, and it coordinates the physiological responses of the entire organism through hormonal signaling. Mutant animals with reduced GH signaling are not only long-lived, but are protected against age-associated decline in memory and learning. Methionine restriction has been shown previously to extend lifespan and delay aging in both rats and mice, dramatically decrease body weight and adiposity, and improve insulin sensitivity and ameliorate aging-associated alterations in glucose and lipid homeostasis. Thus, combing delaying aging models with AD disease models exhibiting various phenotypic effects provides a novel opportunity to develop new models that will allow studies focused on the interaction between aging, metabolism, and neurodegeneration. Our proposed study will determine if suppression of the GH signaling and methionine restriction will prevent development of behavioral, electrophysiological and histopathologic abnormalities of AD phenotype can serve as a model to study the interaction of aging with AD, providing a new level of analysis of the human brain in health and disease.

神经退行性疾病发病的年龄依赖性机制是