# Bioenergetic dysfunction in the aging, injured brain: characterization and intervention with creatine.

> **NIH NIH R21** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $229,500

## Abstract

PROJECT SUMMARY
The purpose of this R21 proposal is to establish the effects of aging and dietary creatine treatment on the
brain's bioenergetic response to injury. Traumatic brain injury (TBI) is a significant problem among older adults.
Older individuals have a higher risk of sustaining a TBI, and worse outcomes than younger adults. However,
very few studies have focused on how aging affects pathological mechanisms in order to develop targets for
treating TBI in older patients. This study will focus on one important mechanism – bioenergetic dysfunction –
since our understanding of how aging affects the brain's bioenergetic response to injury is almost entirely
lacking. The specific aims of this study are 1) to establish the effects of older age on the bioenergetic response
to TBI, and 2) to manipulate the bioenergetic response to TBI with oral creatine supplementation in adult and
aged rats. Creatine is a promising candidate treatment due to its pleioptrophic benefits including cellular
energy buffering and preservation of mitochondrial function. Our studies will use a combination of in vivo
neuroimaging and ex vivo mitochondrial measures to explore the metabolic response to TBI, and to post-TBI
creatine treatment, over a time course from 1-14 days post-injury. We anticipate that successful completion of
these studies will provide new insights into the effects of aging on bioenergetic mechanisms of TBI, and
provide the first proof-of-concept evidence of creatine benefits for brain injury in aging. Given the lack of
approved treatments for TBI, a safe, low-cost dietary intervention to improve outcomes in older individuals
would have a significant positive impact on TBI survivors and their families.

## Key facts

- **NIH application ID:** 10003922
- **Project number:** 5R21AG058052-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** JANNA Leigh HARRIS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $229,500
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003922

## Citation

> US National Institutes of Health, RePORTER application 10003922, Bioenergetic dysfunction in the aging, injured brain: characterization and intervention with creatine. (5R21AG058052-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10003922. Licensed CC0.

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