The Extended Lifespan of Caenorhabditis elegans rsks-1 Mutants Depends on the Peroxisomal Fatty Acid β-Oxidation Enzyme ACOX-1.2

The peroxisome has been implicated in the processes of aging and longevity regulation. Nevertheless, the mechanism by which peroxisomes regulate longevity remains far from fully elucidated. Here, we compared reactive oxygen species (ROS) levels among five long-lived Caenorhabditis elegans mutants using cross-validation with four different ROS probes and observed an increase in hydrogen peroxide (H2O2) levels in rsks-1(ok1255) mutants. Transcriptomic analysis revealed that the genes involved in peroxisomal fatty acid β-oxidation were upregulated in the rsks-1(ok1255) mutants. The imbalance of H2O2 metabolism in the rsks-1(ok1255) mutants was found to be regulated by the peroxisomal fatty acid β-oxidation enzyme ACOX-1.2. Furthermore, lifespan assays and genetic analysis of transgenic strains demonstrated that the increases in autophagy and lifespan observed in long-lived rsks-1(ok1255) mutants were suppressed by acox-1.2 RNAi. These findings uncover a previously unknown role of peroxisomal fatty acid β-oxidation in the regulation of aging and longevity.