Project Details
Description
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.
Status | Active |
---|---|
Effective start/end date | 6/15/22 → 2/28/25 |
Funding
- National Institute on Aging: $502,986.00
- National Institute on Aging: $558,872.00
- National Institute on Aging: $558,872.00
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