Reparative effect of juvenile factors in aging and injury

老龄化和伤害是全球主要的健康问题和因伤害而死亡的问题 随着年龄的增长急剧增加。由于出血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伤害的不利影响，以利于 健康的生活。在这项建议中，我们目标是确定青少年起源的循环因子 能改善成年和老年动物损伤后的结局。建议进行的实验 是基于我们在小鼠失血性休克模型中的发现 (失血性休克损伤；HI)幼鼠与成年小鼠相比具有生存优势。 我们还发现，来自幼鼠血浆的EVS改善了器官功能和存活率 在HI之后。根据这些数据，我们的假设是幼鼠的血浆因子可以 恢复线粒体功能，减轻氧化应激，减少器官功能障碍和死亡 在成年和老年小鼠中接受HI。我们将通过确定保护性的 幼年鼠源性EVS对成年和老年小鼠的影响及其可能机制 哪些幼年血浆因子对成年和老龄小鼠缺氧缺血性脑损伤有有益作用。vbl.使用 5XFAD小鼠我们将确定幼年EVS是否可以减少阿尔茨海默病的病理 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 通过确定与成熟发育有关的分子因素来重振衰老系统。 我们将使用细胞生物学、生化和基因组学工具和技术相结合来测试 假设。我们希望我们的研究将导致对青少年保护性行为的确认 可改善失血性休克后预后的因素。拟议的研究是 与美国国立卫生研究院开发基础知识的任务有关的部分 可能有助于减轻人类疾病的负担。这项研究的结果将是 意义重大，因为从这项研究中获得的基本知识有望取得进展 倡导健康生活的方法。

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.