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.

Aging and injury are among the major global health problems and death due to injury increases sharply with age. Hemorrhage accounts for almost half of trauma-related deaths. In this proposal we seek to identify endogenous juvenile factors that can reduce the adverse influence of aging on outcome following hemorrhagic shock.