Interaction between the ins/IGF-1 and p38 MAPK signaling pathways in molecular compensation of genes and modulation related to intracellular ROS levels in .

Superoxide dismutases, which catalytically remove intracellular superoxide radicals by the disproportionation of molecular oxygen and hydrogen peroxide, are encoded by the to genes in the nematode . Expression of the genes is mutually compensatory for the modulation of intracellular oxidative stress during aging. Interestingly, several-fold higher expression of the to was induced in a deletion mutant, despite the low expression levels of in wild-type animals. Consequently, this molecular compensation facilitated recovery of lifespan in the mutant. In previous reports, two transcription factors DAF-16 and SKN-1 are associated with the compensatory expression of genes, which are downstream targets of the ins/IGF-1 and p38 MAPK signaling pathways activated under oxidative and heavy metal stresses, respectively. Here, we show that p38 MAPK signaling regulates induction of not only the direct expression of , and but also the indirect modulation of DAF-16 targets, such as and genes. Moreover, a SKN-1 target, the insulin peptide gene , partially mediates the expression of DAF-16 targets via p38 MAPK signaling. These findings suggest that the interaction of ins/IGF-1 and p38 MAPK signaling pathways plays an important role in the fine-tuning of molecular compensation among genes to protect against mitochondrial oxidative damage during aging.