Fig. 1

Factors and pathways that regulate immunosenescence in Caenorhabditis elegans. A Upon pathogen infection of aged wild-type C. elegans, downregulation of PMK-1/p38 mitogen-activated protein kinase (MAPK) leads to intestinal damage and immunosenescence. In addition, downregulation of SKN-1/NRF transcription factor decreases the expression of stress-responsive genes and contributes to immunosenescence. B Aged daf-2 mutant C. elegans displays reversed immunosenescence. Genetic inhibition of DAF-2/insulin/IGF-1 receptor upregulates DAF-16/FOXO and HSF-1/heat-shock transcription factor 1. This leads to downregulation of INS-7/insulin-like peptide, which is also regulated by the ZIP-10/bZIP transcription factor, resulting in further reduction of DAF-2 signaling, and reverses immunosenescence