秀丽隐杆线虫 rsks-1 突变体延长寿命的机制依赖于过氧化物体脂肪酸β-氧化酶 ACOX-1.2

Abstract

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 (H 2 O 2 ) 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 H 2 O 2 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.