# Effects of the Muscle Factor Beta-aminoisobutyric acid, BAIBA, in Old and Young Osteocytes

> **NIH NIH P01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $368,944

## Abstract

ABSTRACT
Clearly exercise has beneficial effects on many systems in the body such as neural, metabolic and
musculoskeletal systems, but it is not clear if these benefits delay the effects of aging or if aging blunts the effects
of exercise. Sarcopenia and osteoporosis are major hallmarks of the aging musculoskeletal system resulting in
frailty, falls, fracture, and morbidity. We have shown that muscle and bone communicate systemically through
soluble factors and specifically that muscle secretes low molecular weight factors during contraction that affect
bone. These factors protect osteocytes against cell death induced by either glucocorticoids or by reactive oxygen
species. One of these low molecular weight factors is β-aminoisobutyric acid, BAIBA. This molecule has
previously been shown to induce the browning of white fat and improve insulin resistance. We found that BAIBA
was equal or more potent than n-acetyl cysteine and estrogen to prevent osteocyte cell death. We have begun
to examine the cellular mechanisms responsible for the protective effects of BAIBA against H2O2 and found that
mitochondria are dynamic in osteocytes and that BAIBA prevents their fission and breakdown. BAIBA is
produced by contracted muscle, and whereas both old and young muscle produce BAIBA in response to
contraction, old osteocytes from 22 month old mice are not protected by BAIBA to the same extent as young
osteocytes from 5 month old mice. This suggests that it is not the levels of BAIBA that are defective with exercise
with aging but that aged osteocytes can no longer respond to BAIBA. One receptor for BAIBA, known as the
mas-related G-protein coupled receptor, type D, MRGPRD, was found to be most highly expressed in young
osteocytes, but decreased in old osteocytes which may be why old osteocytes have reduced response to BAIBA.
Our preliminary in vivo experiments where BAIBA is administered in drinking water to hindlimb unloaded 5 mo
old mice suggests that BAIBA can retain not only bone mass but also muscle function. Our hypothesis is: Muscle
in response to exercise produces factors such as BAIBA, that protect bone to maintain bone mass. This
protection of bone by BAIBA is achieved by blocking or reducing the effects of reactive oxygen species,
ROS, through the maintenance of osteocyte mitochondrial dynamics and their function. Exercise
provides the positive effects of BAIBA on the skeleton with aging. To test this hypothesis, the specific aims
of this project are: To determine the molecular mechanism used by BAIBA to protect and preserve bone viability
and bone mass and to determine if BAIBA protects against bone loss and mediates some of the beneficial effects
of exercise on bone and on muscle. Understanding how a low molecular molecule, β-aminoisobutyric acid,
produced by muscle, can block oxidative stress induced osteocyte cell death has the potential to lead to new
therapeutics to prevent both bone and muscle loss with aging. As mitochondrial function in os...

## Key facts

- **NIH application ID:** 10413017
- **Project number:** 5P01AG039355-10
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Lynda F Bonewald
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $368,944
- **Award type:** 5
- **Project period:** 2012-05-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413017

## Citation

> US National Institutes of Health, RePORTER application 10413017, Effects of the Muscle Factor Beta-aminoisobutyric acid, BAIBA, in Old and Young Osteocytes (5P01AG039355-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10413017. Licensed CC0.

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