The Role of Adipose Tissue in Age-dependent Sensitivity to Critical Illness

脂肪组织在年龄依赖性危重疾病敏感性中的作用

基本信息

批准号：
8309139
负责人：
Hiroshi Saito
金额：
$ 30.44万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8309139
关键词：
Abbreviations Acute Adipose tissue Age Age Reporting Aging Animal Model Blood Coagulation Factor Body fat Burn Trauma Cessation of life Coagulants Coagulation Process Complication Critical Illness Death Rate Development Disease Resistance Disseminated Intravascular Coagulation Elderly Endotoxemia Endotoxins Excision Foundations Functional disorder Gene Expression Genes Genetic Goals Growth Factor Health Care Costs Hormones In Vitro Incidence Inflammation Inflammatory Inflammatory Response Injection of therapeutic agent Injury Interleukin-1 Receptors Interleukin-6 Intra-abdominal Knockout Mice Ligation Link Lipopolysaccharides Lung Measures Mediating Mediator of activation protein Methods Modeling Mus Operative Surgical Procedures Organ Organ Culture Techniques Pathway interactions Patients Pattern Plasminogen Activator Inhibitor 1 Plasminogen Activator Inhibitor 2 Plasminogen Inactivators Play Predisposition Preventive Process Production Public Health Puncture procedure Role Sepsis Sepsis Syndrome Severities Signaling Protein Source Stress System TNF gene Testing Therapeutic Thromboplastin Thrombosis Transgenic Organisms Transplantation Visceral Visit Wild Type Mouse acute pancreatitis age related aged biological adaptation to stress cytokine dietary restriction effective therapy improved insight middle age mortality mouse model mutant neglect older patient research study therapy development

项目摘要

DESCRIPTION (provided by applicant): Aging is characterized by an altered stress response that underlies a compromised resistance to disease or injury. Activation of inflammatory and coagulant pathways is a frequent consequence of severe critical illnesses and results in the progression of systemic inflammatory response syndrome (SIRS). Recent evidence suggests that adipose tissue-derived signaling proteins, including cytokines, coagulation factors and hormones, may play an important role in the inflammatory response. Our long-term goals are to identify the mechanisms by which adipose tissue contributes to age-dependent severity of SIRS and to develop therapeutic strategies for decreasing vulnerability to critical illnesses in the aged. For these studies we will use two widely accepted mouse models of SIRS - acute endotoxemia induced by injection with bacterial endotoxin lipopolysaccharide and an intra-abdominal sepsis model induced by cecal ligation and puncture. The objective of this project is to identify and evaluate the expression of adipose-derived inflammatory and coagulant factors that differ by aging upon inflammatory stress. Our central hypothesis is that expression patterns of inflammatory / coagulant factors in the adipose tissue during SIRS are significantly altered by aging and that this alteration contributes to age-dependent severity of critical illnesses. To achieve the above goals, we will pursue the following three specific aims: (1) To define the role of adipose tissue in age-related alterations of coagulation during critical illness. (2) To understand the mechanisms of age-related inflammatory cytokine production in the adipose tissue during critical illness. (3) To evaluate methods of body fat loss as potential therapies and preventative measures for reducing severity of critical illness in the aged. These studies will provide significant insight into the association of the previously neglected adipose organ in aging and critical illness.

描述（由申请人提供）：衰老的特征是应激反应改变，其构成对疾病或损伤的耐药性的构成。炎症和凝结途径的激活是严重危害疾病的常见结果，并导致全身性炎症反应综合征（SIRS）的发展。最近的证据表明，脂肪组织衍生的信号蛋白（包括细胞因子，凝结因子和激素）可能在炎症反应中起重要作用。我们的长期目标是确定脂肪组织对SIRS年龄依赖性严重程度有助于的机制，并制定治疗策略，以减少老年人对重症疾病的脆弱性。在这些研究中，我们将使用两个广泛接受的SIRS的小鼠模型 - 用细菌内毒素脂多糖注射引起的急性内毒素血症，以及由Cecal结扎和穿刺引起的腹腔内败血症模型。该项目的目的是识别和评估脂肪衍生的炎症和凝结因子的表达，这些因素因炎症压力而衰老而有所不同。我们的中心假设是，衰老在SIR中脂肪组织中炎症 /凝结因子的表达模式显着改变，并且这种改变有助于重症疾病的年龄依赖性严重程度。为了实现上述目标，我们将追求以下三个具体目标：（1）定义脂肪组织在重症疾病期间与年龄相关的凝结变化中的作用。（2）了解重病期间脂肪组织中与年龄相关的炎症细胞因子产生的机制。（3）评估人体脂肪流失的方法作为潜在的疗法和预防措施，以降低老年人的严重性严重性。这些研究将对先前被忽视的脂肪器官在衰老和危重疾病中的关联提供重大见解。