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Calorie Restriction, Body Temperature and Alzheimers Disease

热量限制、体温和阿尔茨海默病

基本信息

批准号：
10727319
负责人：
BRUNO CONTI
金额：
$ 29.25万
依托单位：
SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10727319
关键词：
Abbreviations Affect Age Aging Alzheimer like pathology Alzheimer&apos s Disease Alzheimer&apos s disease model Amyloid beta-Protein Animal Model Animals Attenuated Back Bacteria Behavior Behavioral Biochemical Biological Body Temperature Brain Caenorhabditis elegans Caloric Restriction Calories Cognitive Cytoprotection Data Deterioration Diet Disease Environment Equilibrium Evaluation Evolution Exhibits Experimental Models Exploratory/Developmental Grant Female Genetic Glossary Hamsters Hippocampus House mice Housing Human Hypothalamic structure Impaired cognition Incidence Individual Intake Life Extension Longevity Mammals Measures Mediating Memory Memory Loss Modeling Molecular Chaperones Mus Mutation Nature Neurodegenerative Disorders Organism Outcome Pathology Pathway interactions Plasma Post-Translational Protein Processing Proteins Regimen Role Senile Plaques Stress Swedish mutation System Temperature Testing Tg2576 Therapeutic Thermodynamics Transgenic Model Work age effect anti aging cognitive function dietary dietary restriction entorhinal cortex experimental study human model hyperphosphorylated tau male metabolome mimetics misfolded protein mouse model natural hypothermia neuroinflammation neuropathology neuroprotection overexpression phenomenological models prevent protein misfolding proteotoxicity response senescence tau Proteins transgenic model of alzheimer disease virtual young adult

项目摘要

Calorie restriction (CR) has anti-aging effects, prolongs lifespan and reduces the incidence of age associated diseases. Experimental evidence in animal models indicates that CR ameliorates the neuropathologic and behavioral abnormalities seen in transgenic models of Alzheimer’s disease (AD). Our previous work demonstrated that one mechanism by which CR promotes longevity is by reducing core body-temperature (Tb). Since virtually all proteins are sensitive to heat denaturation, nature has created cellular systems to protect cells from even small quantities of abnormally folded toxic proteins as far back in evolution as bacteria. We now hypothesize that the beneficial effects that CR has on the AD models are at least in part due to its ability to reduce Tb and the subsequent proteotoxic stress. Here we propose experiments to test our hypothesis regarding the role of lowering body temperature as being a major factor in both life extension and the salutary effect of CR in the well validated Tg2576 transgenic model of human AD.

热量限制（CR）具有抗衰老作用，延长寿命并降低年龄相关疾病的发生率疾病动物模型中的实验证据表明，CR改善了神经病理学和阿尔茨海默病（AD）转基因模型中观察到的行为异常。我们以前的工作证明CR促进长寿的一种机制是通过降低核心体温（Tb）。由于几乎所有的蛋白质都对热变性敏感，自然界创造了细胞系统来保护细胞甚至是少量的异常折叠的有毒蛋白质，早在细菌的进化过程中就有了。我们现在假设CR对AD模型的有益作用至少部分是由于其能够减少Tb和随后的蛋白毒性应激。在这里，我们提出实验来测试我们的假设，降低体温的作用是延长寿命和CR有益效果的主要因素在人AD的充分验证的Tg2576转基因模型中。