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。研究表明， 骨髓间充质干细胞(MSC)和细胞外小泡(EVS)的培养上清 在组织损伤后具有保护性。这个项目中提出的实验是基于 我们在失血性休克小鼠模型(失血性休克损伤；HI)中的发现 与成年小鼠相比，幼年小鼠具有生存优势。我们的研究还表明， 来自骨髓间充质干细胞培养上清和幼鼠血浆的EVS可以改善 成年小鼠的存活率。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 成年和老龄小鼠缺氧缺血后的功能障碍和死亡。我们将通过以下方式验证我们的假设 幼年鼠源性EVS对成年和老年小鼠的保护作用及鉴定 青少年血浆因子对成年期和老年人有益作用的可能机制 小鼠紧随HI。我们的目标是开发方法，通过确定 参与成熟发育的分子因素。我们将使用细胞的组合 生物、生物化学和基因组学工具和技术来检验这一假说。我们期待着 我们的研究将导致确定可以改善结果的青少年保护因素 在失血性休克之后。这项拟议的研究与美国国立卫生研究院的部分任务有关 关于开发基础知识以潜在地帮助减轻人类负担的 疾病。这项研究的结果将具有重要意义，因为基础知识 通过这项研究，有望提出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.