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Aging‐Dependent Shift in Hepatic GGA Biosynthesis: A Proposed Axis Involving MAOB and CYP3A4 in Liver Cancer Susceptibility

by Yuki Tabata

Posted: June 24, 2025
Server: Preprints.org
DOI: 10.20944/preprints202506.1957.v1

Geranylgeranoic acid (GGA) is a naturally occurring acyclic isoprenoid with chemopreventive effects against hepatocellular carcinoma. In mammals, GGA is endogenously synthesized via the oxidative metabolism of geranylgeraniol by monoamine oxidase B (MAOB). However, MAOB activity decreases with age, leading to reduced hepatic GGA levels. Emerging evidence suggests that cytochrome P450 3A4 (CYP3A4) may compensate for this decline, providing an alternative oxidative pathway in MAOB-deficient conditions. This mini-review summarizes the current findings on GGA biosynthesis and metabolism in the aging liver, focusing on the MAOB-CYP3A4 axis and its relevance to age-related hepatic dysfunction. By discussing recent evidence on enzymatic compensation and age-dependent metabolic changes, this review highlights how the CYP3A4-GGA pathway may help unravel the complexity of hepatic aging.

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