image: Figure 9. EDL muscle fiber cross-sectional area after the three-month intervention period. (A) Representative images of EDL muscle histological sections stained for dystrophin for quantitation of myofibers. The scale bar represents 100 μm. (B) Quantitation of the total number of EDL myofibers. (C) Average EDL myofiber cross-sectional area (CSA). (D) The frequency distribution of EDL myofiber CSA. Inlay: Superimposed myofiber frequency distribution curves at 250 μm binning. Two-way ANOVA, p>0.05. n = 8 CTRL, n = 8 VWR, n = 8 CTRL+L-BAIBA, n = 8 VWR+L-BAIBA. Mean ± SD.
Credit: Copyright: © 2025 Vallejo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“These findings suggest a physiological interaction between exercise and L-BAIBA supplementation to improve soleus muscle and bone properties and reduce bone marrow adiposity.”
BUFFALO, NY — November 11, 2025 — A new research paper was published in Volume 17, Issue 10 of Aging-US on October 1, 2025, titled “L-β-aminoisobutyric acid (L-BAIBA) in combination with voluntary wheel running exercise enhances musculoskeletal properties in middle-age male mice.”
In this study led by first author Julian A. Vallejo and corresponding author Michael J. Wacker from the University of Missouri, Kansas City, researchers investigated how L-β-aminoisobutyric acid (L-BAIBA), a natural compound released during exercise, works together with regular physical activity to improve muscle and bone health in middle-aged male mice. The findings may support new strategies to maintain musculoskeletal health in aging populations, especially those at risk for mobility loss or osteoporosis.
Muscle and bone strength naturally decline with age, increasing the risk of falls, fractures, and reduced quality of life. While exercise remains the most effective way to counteract this deterioration, it is often difficult for older individuals to maintain sufficient activity levels to see results. L-BAIBA, a molecule naturally produced during physical activity, is known to promote energy metabolism and support muscle and bone cells. This study explored its potential to work in synergy with endurance exercise to maximize health benefits in aging bodies.
Researchers studied 12-month-old male mice that were split into different groups. Some remained sedentary, while others exercised freely on running wheels. Half of each group received daily L-BAIBA supplementation. After three months, the mice that received both the supplement and exercise showed greater improvements than those receiving either one alone. The soleus, a slow-twitch muscle essential for endurance and balance, grew larger and stronger only in the combined treatment group. These muscles also shifted to a more fatigue-resistant fiber type and had a larger number of oxidative fibers.
“To investigate this hypothesis, we subjected 12-month-old (as a model of middle-age) male C57BL6 mice to voluntary wheel running (VWR) with L-BAIBA (100mg/kg/day) (VWR+L-BAIBA), VWR alone, L-BAIBA alone, or none (CTRL) for three months.”
The study also showed significant improvements in bone health. Mice that received both exercise and L-BAIBA developed thicker and denser trabecular bone, along with reduced fat levels in the bone marrow, indicators of stronger, healthier bones. These changes were not observed in the groups that only exercised or only received L-BAIBA. Although the compound caused minor changes in heart electrical activity, it did not affect heart size or overall function, suggesting it is safe in this setting.
These findings suggest that L-BAIBA may enhance the benefits of physical activity by supporting muscle strength and bone structure, particularly in slow-twitch muscle fibers. This combination could serve as a therapeutic strategy to help older adults, including those unable to engage in regular exercise, maintain musculoskeletal health.
As the aging population grows, there is a growing need for solutions that support muscle and bone health without requiring strenuous activity. This research highlights the potential of natural, exercise-related molecules like L-BAIBA to help maintain mobility and strength throughout aging.
Read the full paper: DOI: https://doi.org/10.18632/aging.206325
Corresponding author: Michael J. Wacker – wackerm@umkc.edu
Abstract video: https://www.youtube.com/watch?v=A-zfrLUikfQ
Keywords: endurance exercise, dietary supplementation, musculoskeletal adaptation, electrocardiogram, aging
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
L-β-aminoisobutyric acid (L-BAIBA) in combination with voluntary wheel running exercise enhances musculoskeletal properties in middle-age male mice
Article Publication Date
1-Oct-2025
COI Statement
The authors declare no conflicts of interest related to this study.