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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：
8852028
负责人：
Hiroshi Saito
金额：
$ 29.53万
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 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8852028
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 Chips Genes Genetic Goals Growth Factor Health Care Costs Hormones In Vitro Incidence Inflammation Inflammatory Inflammatory Response Injection of therapeutic agent Injury Interleukin-1 Interleukin-1 Receptors Interleukin-6 Intra-abdominal Knockout Mice Ligation Link Lipopolysaccharides Lung Measures Mediating Mediator of activation protein Methods Microarray Analysis 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的改变，这是对疾病或损伤的抵抗力受损的基础。炎症和凝血途径的激活是严重危重疾病的常见后果，并导致全身炎症反应综合征（SIRS）的进展。最近的证据表明，脂肪组织来源的信号蛋白，包括细胞因子，凝血因子和激素，可能在炎症反应中发挥重要作用。我们的长期目标是确定脂肪组织导致SIRS严重程度与年龄相关的机制，并制定治疗策略以降低老年人对重症疾病的易感性。对于这些研究，我们将使用两种广泛接受的SIRS小鼠模型-通过注射细菌内毒素脂多糖诱导的急性内毒素血症和通过盲肠结扎和穿刺诱导的腹腔内脓毒症模型。本项目的目的是识别和评估脂肪源性炎症和凝血因子的表达，这些因子在炎症应激时因年龄而异。我们的中心假设是，炎症/凝血因子在脂肪组织中的表达模式在全身炎症反应综合征过程中显着改变了老化，这种改变有助于年龄依赖性的严重疾病的严重程度。为了实现上述目标，我们将追求以下三个具体目标：（1）确定脂肪组织在危重病期间与年龄相关的凝血变化中的作用。(2)了解危重病期间脂肪组织中与年龄相关的炎性细胞因子产生的机制。(3)评估减脂方法作为降低老年危重病严重程度的潜在治疗和预防措施。这些研究将为以前被忽视的脂肪器官与衰老和重症疾病的关联提供重要见解。