A pilot study to determine if L-beta aminoisobutyric acid, L-BAIBA, can serve as a marker of muscle and mitochondrial function. Sarcopenia (loss of muscle) and osteoporosis (loss of bone) are major hallmarks of musculoskeletal aging, and result in frailty, falls, fractures, 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 other tissues including bone. One of these low molecular weight factors is ?-aminoisobutyric acid, BAIBA. This suggests that it is not the levels of BAIBA that are defective with aging, but that aged osteocytes can no longer respond to BAIBA. BAIBA is produced by exercise. We have found in preclinical studies that it reduces the death of the most abundant bone sensing cells, osteocytes, due to the reactive oxygen species, known to be elevated with aging. However, the benefits varied by animal age. Muscle in both old and young animals produce BAIBA in response to contraction, but osteocytes from old (22 month old) mice were not protected by BAIBA to the same extent as osteocytes from young (5 month old) mice. This suggests that it is not the levels of BAIBA that are defective with aging, but that aged osteocytes can no longer respond to BAIBA. BAIBA is produced in the body as either a D or and L enantiomer (Vemula et al, Analytical Chemistry, 2017). The L form is derived from valine through the actions of PCG1a and other enzymes in muscle. The D form appears to be derived from thymine and may be produced by the liver but the source/s is/are not clear. When we compared the D and L forms, we found that the L form is about 1000 fold more potent in protecting osteocytes against reactive oxygen species (ROS)- induced cell death (Kitase et al, Cell Reports, 2018). We also found that L-BAIBA was protective against muscle loss with hindlimb unloading (Kitase et al, Cell Reports, 2018). Studies by other investigators have used a mixture of enantiomers (Begriche, 2008; Roberts, 2014; Jung, 2015; Shi, 2016). Ours will be the first study to examine expression of the enantiomers in high performer and low performer humans.
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