权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Vulnerability to sepsis in old age

老年时容易患败血症

基本信息

批准号：
7415043
负责人：
Hiroshi Saito
金额：
$ 21.05万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-15 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7415043
关键词：
Accounting Affect Age Aging Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antioxidants Cause of Death Cessation of life Characteristics Clinical Trials Coagulants Coagulation Process Doctor of Philosophy Elderly Endotoxemia Endotoxins Enzymes Foundations Functional disorder Future Gene Expression Genes Goals Heart Homeostasis Incidence Infection Inflammation Inflammatory Injection of therapeutic agent Intensive Care Units Intervention Intra-abdominal Kidney Ligation Lipopolysaccharides Liver Lung Mediator of activation protein Messenger RNA Modeling Morbidity - disease rate Multiple Organ Failure Mus Mutant Strains Mice Organ Oxidative Stress Patients Population Proteins Puncture procedure Research Research Personnel Risk Role Saline Sepsis Sepsis Syndrome Septic Shock Spleen Testing Tissues age effect aged base improved innovation interest juvenile animal middle age mortality mouse model novel therapeutics older patient research study response septic

项目摘要

DESCRIPTION (provided by applicant): Sepsis is an infection-initiated manifestation of the systemic inflammatory response syndrome that often progresses to septic shock, multiple organ failure with high risks of death. Sepsis is a particularly serious problem in the geriatric population, as the elderly patients with sepsis suffer much higher morbidity and mortality than younger patients. In fact, sepsis is a major cause of death in elderly patients at intensive care units in the US. Although this problem is increasingly recognized, the underlying mechanism(s) responsible for this age-associated vulnerability remain largely unknown. The long-term goal of our research is to determine the mechanisms responsible for the increased septic vulnerability in the aged, and to use this information to develop new treatment strategies for sepsis. The age-associated vulnerability to sepsis is also seen in animal models. We have shown that aged mice suffer significantly higher mortality than young mice in two commonly used models for sepsis; endotoxemia induced by bacterial lipopolysaccharide injection, and an intra-abdominal sepsis induced by cecal ligation and puncture. We have also found that the elevated mortality in aged mice is associated with altered inflammatory and coagulation responses, and increased oxidative damages. Our central hypothesis is that loss of homeostasis in old age leads to excessive inflammation, oxidative damage, and coagulation, contributing to the age-associated vulnerability to sepsis. Our objective in this project is to define the age-associated alterations in pathophysiology and gene expression in the mouse model of sepsis, and to develop strategies to improve the survival of the old mice with sepsis. To achieve these goals, we pursue the following three specific aims: (1) To determine the effects of aging on the pathophysiology of sepsis, (2) To identify the age-associated alterations in gene expression that affects mortality in sepsis, and (3) To test likely strategies for their ability to decrease age-associated mortality in sepsis. The information obtained from this project should provide the basis for new therapeutic strategies to substantially decrease the mortality in elderly patients with sepsis.

描述（由申请人提供）：