Kynurenine, a Tryptophan Metabolite That Increases with Age, Induces Muscle Atrophy and Lipid Peroxidation

Figure 5

Proposed model for KYN’s effects on lipid peroxidation, ROS generation, and age-related muscle atrophy. Aging causes an increase in systemic oxidative stress, and skeletal muscle antioxidant pathways are unable to meet the increased demand. Inflammatory cytokines like IFNγ activate IDO to convert tryptophan to KYN. KYN then induces the upregulation of mitochondrial VLCADm which degrades lipid and produces H₂O₂. The overexpression of ROS leads to further inflammation and muscle atrophy. 1-MT is an antagonist of IDO that can inhibit tryptophan’s conversion into KYN, thereby attenuating KYN-induced tissue dysfunction with aging.