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。研究表明 间充质干细胞（MSC）和来自MSC培养上清液的细胞外囊泡（EV 在组织损伤后起到保护作用。本项目中提出的实验是基于 我们发现在小鼠模型中失血性休克（出血性休克损伤; HI）后， 与成年小鼠相比，幼年小鼠具有存活优势。我们的研究还表明， 来源于MSC培养上清液和年轻小鼠血浆的EV可以改善 在成年小鼠中存活。根据这些数据，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，减轻氧化应激，减少器官 在经历HI的成熟和老年小鼠中的功能障碍和死亡。我们将测试我们的假设， 确定幼年小鼠来源的EV在成年和老年小鼠中的保护作用，并鉴定 幼年血浆因子在成年和老年人中发挥有益作用的潜在机制 HI后小鼠。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。我们将使用细胞的组合 生物学、生物化学和基因组学工具和技术来检验这一假设。我们预计 我们的研究将导致识别青少年保护因素，可以改善结果 失血性休克后拟议的研究与NIH的部分使命相关 关于发展基础知识，以潜在地帮助减轻人类负担， 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信息有望推动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. 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.