(A) The age-related changes in gene expression profiling on hippocampal tissue obtained from WT as well as Nlrp3 and Asc mutant mice. (B) A set of 298 gene probes that respond to aging, and are modulated by loss of Nlrp3 and Asc. (C) Examination of the direction of change revealed that nearly all (295 of 298) gene probes with expression differences between old and young WT (blue bars) show expression changes in the opposite direction when comparing old mutant to old WT. (D, E) Pathway analyses of genes with age-dependent expression differences reveal a strong enrichment of genes related to cell death as well as to inflammatory disease in WT mice compared to Nlrp3 and Asc mutants. Similar differences in association were found for NF-kB, IL-1, and IL-8 signaling, where the respective pathways were found to be strongly associated with age-dependent expression differences in WT mice compared to Nlrp3−/− and Asc−/− animals. (F) The list of genes (p<0.05, 1.5 fold change) that are involved in cell death and inflammation and regulated by both Nlrp3 and Asc during aging. This pattern suggests that these group of genes are characterized by age-dependent gene expression changes which is regulated by the absence of the Nlrp3 inflammasome activity. See also Figure S5.