Reparative effect of juvenile factors in aging and injury

幼年因素对衰老和损伤的修复作用

基本信息

批准号：
10445560
负责人：
Raghavan Pillai Raju
金额：
$ 31.57万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10445560
关键词：
Acute Adolescent Adult Adverse effects Age Aging Animals Antioxidants Autophagocytosis Biological Biology of Aging Cell Culture Techniques Cells Cessation of life Data Development Elderly Equilibrium Functional disorder Gene Expression Genes Goals Heart Hemorrhage Hemorrhagic Shock Hypoxia Injury Intestines Knowledge Liver Longevity Lung Mesenchymal Stem Cells Metabolic Methods MicroRNAs Mission Mitochondria Molecular Morbidity - disease rate Mus Organ Outcome Outcomes Research Oxidative Stress Plasma Rattus Reporting Research Resuscitation SIRT1 gene System Techniques Testing Therapeutic Time Trauma United States National Institutes of Health age effect aged animal age group base biochemical tools compare effectiveness experimental study extracellular vesicles functional decline genomic tools global health human disease human old age (65+)improved improved outcome juvenile animal mortality mouse model protective effect protective factors resilience response tissue injury

项目摘要

Aging and injury are among the major global health problems and death due to injury increases sharply with age. As hemorrhage accounts for almost half of all trauma-related deaths, there is a need to develop methods to reduce the adverse effects of aging on injury to facilitate healthy living. In this proposal, our objective is to establish that circulatory factors of juvenile origin can improve outcome following injury in the mature and aged animals. Studies show that mesenchymal stem cells (MSC) and extracellular vesicles (EVs) from MSC culture supernatant are protective following tissue injuries. The experiments proposed in this project are based upon our finding that following hemorrhagic shock in a mouse model (hemorrhagic shock injury; HI) juvenile mice have a survival advantage compared to adult mice. Our studies also indicate that EVs derived from MSC culture supernatants and from the plasma of young mice can improve survival in adult mice. Based upon these data our hypothesis is that plasma factors from juvenile animals can restore mitochondrial function, alleviate oxidative stress and reduce organ dysfunction and death in mature and old mice subjected to HI. We will test our hypothesis by determining the protective effect of juvenile mice-derived EVs in mature and old mice and identify potential mechanisms by which juvenile plasma factors exert salutary effect in mature and aged mice following HI. Our goal is to develop methods to revitalize the aging system by identifying molecular factors involved in maturational development. We will use a combination of cell biological, biochemical and genomic tools and techniques to test the hypothesis. We expect that our studies will result in the identification of juvenile protective factors that can improve outcome following hemorrhagic shock. The proposed research is relevant to the part of NIH’s mission pertaining to developing fundamental knowledge to potentially help reduce the burdens of human disease. The outcome of this research will be significant because the fundamental knowledge gained from this study is expected to advance methods to promote healthy living.

衰老和受伤是由于受伤而导致的主要全球健康问题和死亡随着年龄的增长而急剧增加。由于出血几乎占所有与创伤有关的死亡的一半，有必要开发方法来减少衰老对损伤的不利影响以促进健康的生活。在此提案中，我们的目标是确定少年起源的电路因素成熟和老年动物受伤后可以改善结果。研究表明 MSC培养物上清液中的间充质干细胞（MSC）和细胞外蔬菜（EV）在组织损伤后受到保护。该项目中提出的实验是基于我们的发现，在小鼠模型中发生出血性休克（出血性休克损伤； HI）与成年小鼠相比，青少年小鼠具有生存优势。我们的研究还表明来自MSC培养上清液和年轻小鼠血浆的电动汽车可以改善成年小鼠的生存。基于这些数据，我们的假设是青少年的血浆因子动物可以恢复线粒体功能，减轻氧化物应激并减少器官受HI的成熟和老鼠的功能障碍和死亡。我们将通过确定成熟和旧小鼠中少年小鼠衍生的电动汽车的受保护作用，并识别少年血浆因子因成熟和老化发挥活力效应的潜在机制小鼠跟随嗨。我们的目标是开发方法来通过识别来振兴衰老系统涉及成熟发展的分子因素。我们将使用单元组合生物学，生化和基因组工具以及检验该假设的技术。我们期望这一点我们的研究将导致识别少年保护因素，以改善结果发生出血性休克。拟议的研究与NIH任务的一部分有关与发展基本知识有关以有助于减少人类的伯恩斯的知识疾病。这项研究的结果将是重要的，因为基本知识从这项研究中获得的预计将推进促进健康生活的方法。