Enhanced Branched-Chain Amino Acid Metabolism Improves 7 Age-Related Reproduction

Reproductive aging is one of the earliest human aging phenotypes, and mitochondrial dysfunction has been linked to a decline in oocyte quality. However, it is not known which mitochondrial metabolic processes are critical for oocyte quality maintenance with age. To understand how mitochondrial processes contribute to C. elegans oocyte quality, we characterized the mitochondrial proteomes of young and aged wild-type and long-reproductive daf-2 mutants. The mitochondrial proteomic profiles of young wild-type and daf-2 worms are similar and share upregulation of branched-chain amino acid (BCAA) metabolism pathway enzymes. Reduction of bcat-1 shortens reproduction, elevates mitochondrial ROS levels, and shifts mitochondrial localization. Moreover, bcat-1 knockdown decreases daf-2’s oocyte quality and reduces reproductive capability, indicating the importance of this pathway in the maintenance of oocyte quality with age. Importantly, we can delay oocyte quality deterioration and extend reproduction in wild-type animals both by bcat-1 overexpression and by supplementing with Vitamin B1, a cofactor needed for BCAA metabolism.