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: 10445560
• 负责人: Raghavan Pillai Raju
• 金额: $ 31.57万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10445560
• 关键词: Acute; Adolescent; Adult; Adverse effects; Age; Aging; Animals; Antioxidants; Autophagocytosis; Biological; Biology of Aging; Cell Culture Techniques; Cells; Cessation of life; Data; Development; Elderly; Equilibrium; Functional disorder; Gene Expression; Genes; Goals; Heart; Hemorrhage; Hemorrhagic Shock; Hypoxia; Injury; Intestines; Knowledge; Liver; Longevity; Lung; Mesenchymal Stem Cells; Metabolic; Methods; MicroRNAs; Mission; Mitochondria; Molecular; Morbidity - disease rate; Mus; Organ; Outcome; Outcomes Research; Oxidative Stress; Plasma; Rattus; Reporting; Research; Resuscitation; SIRT1 gene; System; Techniques; Testing; Therapeutic; Time; Trauma; United States National Institutes of Health; age effect; aged; animal age group; base; biochemical tools; compare effectiveness; experimental study; extracellular vesicles; functional decline; genomic tools; global health; human disease; human old age (65+); improved; improved outcome; juvenile animal; mortality; mouse model; protective effect; protective factors; resilience; response; tissue injury

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.

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损伤的不利影响，以促进 健康生活。在本提案中，我们的目标是确定幼年起源的循环因子 可以改善成熟和老年动物受伤后的结果。研究表明 来自 MSC 培养上清液的间充质干细胞 (MSC) 和细胞外囊泡 (EV) 在组织损伤后具有保护作用。该项目中提出的实验基于 我们的发现是，在小鼠模型中发生失血性休克（失血性休克损伤；HI） 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 源自 MSC 培养上清液和幼鼠血浆的 EV 可以改善 成年小鼠的存活率。根据这些数据，我们的假设是，来自青少年的血浆因子 可以恢复动物线粒体功能，缓解氧化应激，减少器官功能 遭受 HI 的成熟和老年小鼠的功能障碍和死亡。我们将通过以下方式检验我们的假设 确定幼年小鼠来源的 EV 对成熟和老年小鼠的保护作用并鉴定 青少年血浆因子对成熟和老年人发挥有益作用的潜在机制 HI 后的小鼠。我们的目标是通过识别来开发振兴衰老系统的方法 参与成熟发育的分子因素。我们将使用单元格的组合 检验假设的生物学、生化和基因组工具和技术。我们期望 我们的研究将确定可以改善结果的青少年保护因素 失血性休克后。拟议的研究与 NIH 的部分使命相关 有关发展基础知识以潜在帮助减轻人类负担 疾病。这项研究的结果将是意义重大的，因为基础知识 这项研究的成果预计将推进促进健康生活的方法。

项目成果

Juvenile Plasma Factors Improve Organ Function and Survival following Injury by Promoting Antioxidant Response.

• DOI: 10.14336/ad.2021.0830
• 发表时间: 2022-04
• 期刊: Aging and disease
• 影响因子: 7.4
• 作者: Chu X;Subramani K;Thomas B;Terry AV Jr;Fulzele S;Raju RP
• 通讯作者: Raju RP