GeroScience · 9 authors, 4 centres
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Male mice subjected to dietary sulfur amino acid restriction (SAAR) showed increased synthesis of fatty acid oxidation proteins and decreased synthesis of amino acid metabolic proteins in the liver, alongside dynamic remodeling of ribosomal and ribosome-associated proteins. These changes were largely agnostic to dietary fat content and are compatible with a slowed growth phenotype linked to improved healthspan.
Male mice were subjected to dietary sulfur amino acid restriction (SAAR), comprising zero cysteine and approximately 80% reduction in methionine, under both low-fat and high-fat diet conditions. Kinetic proteomics using deuterium-labeled alanine and transcriptomic analyses were performed on liver tissue. Dietary SAAR increased synthesis of fatty acid oxidation proteins, decreased synthesis of amino acid metabolic proteins, and induced remodeling of proteins involved in ROS handling and NAD+ metabolism. Synthesis of ribosomal proteins (RPs) and ribosome-associated proteins (RAPs) was significantly altered, indicating restructuring of the ribo-interactome. Although ISR transcriptomic activation was confirmed, no hallmark ISR proteins were detected in the kinetic proteomic dataset, likely because ISR targets have short half-lives or low abundance. No differences in whole liver lysate NAD+/NADH ratios were detected.
