FIGURE 2.
Age-dependent shift in hepatic GGA metabolism and its association with tumorigenesis. In young livers (left), monoamine oxidase B (MAOB) is highly expressed and efficiently converts geranylgeraniol (GGOH) to geranylgeranoic acid (GGA), which activates Toll-like receptor 4 signaling and contributes to tumor-suppressive homeostasis. In aged livers (right), the decline or loss of MAOB represents a metabolic turning point, leading to a marked reduction in hepatic GGA levels and the breakdown of tumor-suppressive homeostasis. Although cytochrome P450 3A4 (CYP3A4) partially compensates for this loss, the insufficient GGA levels fail to maintain adequate tumor suppression, resulting in a more tumor-permissive hepatic microenvironment and increased risk of hepatocellular carcinoma.
