Reparative effect of juvenile factors in aging and injury

幼年因素对衰老和损伤的修复作用

• 批准号: 10642834
• 负责人: Raghavan Pillai Raju
• 金额: $ 55.89万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642834
• 关键词: Acute; Address; Adolescent; Adult; Adverse effects; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Animals; Antioxidants; Autophagocytosis; Biological; Biological Models; Biology of Aging; Cells; Cessation of life; Data; Deterioration; Development; Disease model; Elderly; Equilibrium; Exhibits; Experimental Models; Functional disorder; Gene Expression; Genes; Goals; Heart; Hemorrhage; Hemorrhagic Shock; Hypoxia; Impaired cognition; Injury; Intestines; Knowledge; Liver; Longevity; Lung; Methods; MicroRNAs; Mission; Mitochondria; Modeling; Molecular; Morbidity - disease rate; Mus; Neurodegenerative Disorders; Organ; Outcome; Outcomes Research; Oxidative Stress; Pathology; Pathway interactions; Patients; Plasma; Published Comment; Rattus; Research; Role; SIRT1 gene; Sex Differences; Sexual Maturation; System; Techniques; Testing; Therapeutic; Time; Trauma; Traumatic injury; United States National Institutes of Health; age effect; age group; aged; biochemical tools; cognitive function; comorbidity; disability; effective therapy; exosome; experimental study; extracellular vesicles; functional decline; genomic tools; global health; high risk; human disease; human old age (65+); improved; improved outcome; juvenile animal; mitochondrial dysfunction; mortality; mouse model; older patient; protective effect; protective factors; resilience; response

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. 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. We also found that EVs from the plasma of juvenile mice improved organ function and survival following HI. Based upon these data our hypothesis is that plasma factors from juvenile mice 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. Using 5XFAD mice we will determine whether juvenile EVs can reduce pathology in Alzheimer’s disease, an age associated neurodegenerative disease. 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.

衰老和伤害是全球主要的健康问题以及因伤害而死亡的问题之一 随着年龄的增长，出血导致的死亡人数几乎占所有创伤相关死亡的一半， 有必要开发方法来减少衰老对损伤的不利影响，以促进 在这项提案中，我们的目标是确定青少年起源的循环因素。 可以改善成熟和老年动物受伤后的结果。 在这个项目中基于我们的发现，在小鼠模型中失血性休克后 （失血性休克损伤；HI）幼年小鼠与成年小鼠相比具有生存优势。 我们还发现，来自幼年小鼠血浆的 EV 可以改善器官功能和存活率 根据这些数据，我们的假设是来自幼年小鼠的血浆因子可以 恢复线粒体功能，缓解氧化应激，减少器官功能障碍和死亡 我们将通过确定保护性来检验我们的假设。 幼年小鼠来源的 EV 对成熟和老年小鼠的影响，并通过以下方法确定潜在机制 哪些幼年血浆因子对 HI 后的成熟和老年小鼠发挥有益作用。 我们将通过 5XFAD 小鼠确定幼年 EV 是否可以减少阿尔茨海默病的病理学 疾病，一种与年龄相关的神经退行性疾病，我们的目标是开发方法来治疗。 通过识别参与成熟发育的分子因素来振兴衰老系统。 我们将结合使用细胞生物学、生化和基因组工具和技术来测试 我们期望我们的研究能够确定青少年的保护作用。 可以改善失血性休克后预后的因素。 与 NIH 使命的一部分相关，即发展基础知识 可能有助于减轻人类疾病的负担。 意义重大，因为从这项研究中获得的基础知识有望推进 促进健康生活的方法。