Reparative effect of juvenile factors in aging and injury

衰老和损伤是全球主要的健康问题之一，也是损伤导致的死亡 随着年龄的增长而急剧增加。由于出血几乎占所有创伤相关死亡的一半， 需要开发减少老化对损伤的不利影响的方法 健康的生活在这个建议中，我们的目标是建立幼年起源的循环因素， 可以改善成年和老年动物损伤后的结果。提出的实验 在这个项目中是基于我们发现，在小鼠模型中， （出血性休克损伤; HI）幼年小鼠与成年小鼠相比具有存活优势。 我们还发现，来自幼年小鼠血浆的EV改善了器官功能和存活率。 在HI之后基于这些数据，我们的假设是幼年小鼠的血浆因子可以 恢复线粒体功能，减轻氧化应激，减少器官功能障碍和死亡 在经历HI的成熟和老年小鼠中。我们将通过确定保护性的 幼龄小鼠衍生EV在成熟和老年小鼠中的作用，并通过 其中幼年血浆因子对HI后的成年和老年小鼠有有益作用。使用 5XFAD小鼠，我们将确定青少年EV是否可以减少阿尔茨海默氏症的病理 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， 通过识别参与成熟发育的分子因素来振兴衰老系统。 我们将使用细胞生物学、生物化学和基因组学工具和技术的组合来测试 假设。我们希望我们的研究将导致识别青少年保护性 可以改善失血性休克预后的因素。拟议的研究是 与NIH的使命有关的部分是发展基础知识， 可能有助于减轻人类疾病的负担。这项研究的结果将是 重要的是，从这项研究中获得的基础知识有望提高 促进健康生活的方法。

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.