# Project 1 - Selective amino-acid supplementation to reverse age-induced bone loss

> **NIH NIH P01** · AUGUSTA UNIVERSITY · 2020 · $341,005

## Abstract

This is a competitive renewal of our currently funded project that focused on the impact of dietary amino acids
on bone marrow mesenchymal stem cell (BMSC) function. Our data demonstrates that amino acids have
varying anabolic or catabolic effects. There are 20 common dietary amino acids and our data demonstrates
that the aromatic amino acids have the most potent anabolic effects, particularly in the aging mouse model.
Aging (24-month-old) C57BL/6 mice fed a low protein diet lose bone but this loss is prevented by dietary
supplementation of aromatic amino acids. Our central hypothesis is that AAs are not just fuel, broken down to
provide ATP for cell function, but rather that AAs normally function as “nutritional hormones” binding to
extracellular receptors and activating cell signaling pathways. Our data are consistent with the aging process
resulting in the loss of the ability of BMSCs to “sense” these normal anabolic signals from nutrients through
epigenetic mechanisms. Further aging is associated with the accumulation of toxic breakdown products of
these metabolites that interfere with their normal anabolic actions. We propose to characterize these nutrient
related changes so as to develop effective countermeasures. Therefore, the specific aims of the proposal are:
(1) Test the hypothesis that age-induced epigenetic changes in stem cells resulting in impaired function can be
reversed by dietary interventions; and (2) Test the hypothesis that age-induced epigenetic changes in stem
cells resulting in impaired function can be reproduced by dietary interventions. This project also will explore
synergize with the other projects included in this application looking at effects of these amino acids and
metabolites in aging muscle (Project 2), inflammatory cytokines (Project 3) and histone deacetylation (Project
4).

## Key facts

- **NIH application ID:** 9902285
- **Project number:** 5P01AG036675-09
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** CARLOS M. ISALES
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $341,005
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902285

## Citation

> US National Institutes of Health, RePORTER application 9902285, Project 1 - Selective amino-acid supplementation to reverse age-induced bone loss (5P01AG036675-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9902285. Licensed CC0.

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