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bioRxiv · 10.1101/2025.10.30.685560

Effect of Age and Sex on BCAA Metabolism in Mice

Mann, G.·Mora, S.·Adegoke, O. A. J.
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Abstract

Increased plasma levels of branched-chain amino acids (BCAA) have been implicated in insulin resistance. This condition worsens with age, but plasma BCAA levels are downregulated in old men. The effect of age and/ sex on BCAA metabolism has been rarely studied. Thus, the objective of this study was to analyze how age and sex affect BCAA levels and their metabolism in mouse tissues. Male and female young (4-month) and old (18-months) CD2F1 mice were used. BCAA levels and relevant BCAA metabolic enzymes abundance/activity in plasma, muscle, liver, adipose tissue, and heart were analyzed. Old males exhibited greater plasma BCAA concentrations compared to young males and old females, but plasma branched-chain ketoacid (BCKA) levels were lower in old mice in both sexes. Intracellular BCAA levels were lower in skeletal muscle and heart from old mice independent of sex. There was an age-sex interaction in the lever in that reduced total BCAA was seen only in old male animals. In adipose tissue, total BCKA levels were higher in old male animals. Skeletal muscle abundance of the BCAA transporter LAT1 was reduced in old females compared to young females. In the liver, female mice had higher levels of LAT1 than male mice independent of age, while total BCKD was reduced in old females compared to old males. Pp2Cm levels were reduced in old animals independent of sex. In conclusion, while there were some changes in plasma and tissue BCAA/BCKA levels in response to age/sex, such changes were largely not consistent with changes in tissue BCAA catabolic enzyme abundance/activity. This suggests that protein levels of BCAA catabolic enzymes are preserved in aging in healthy animals and likely only become dysregulated in disease states.

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Mann, G., Mora, S., Adegoke, O. A. J.. 2025-10-31. Effect of Age and Sex on BCAA Metabolism in Mice. https://doi.org/10.1101/2025.10.30.685560

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