Extended Data Fig. 10 |. Transcriptomics of primary peritoneal macrophages from young and aged mice treated with vehicle or with the non-brain-penetrant EP2 inhibitor PF-04418948.

Data are mean ± s.e.m. unless otherwise specified. a, Heat map of 1448 genes from Nanostring assay reveals that aged mice treated with PF-04418948 cluster with young mice treated with vehicle or PF-04418948. b, Volcano plot of peritoneal macrophages collected from aged versus young vehicle-treated mice. Red dots indicate genes that are absolute-value[log₂(FC)] ≥ 2 and FDR < 0.05 by t-test with Benjamini–Hochberg correction. c, Volcano plot of peritoneal macrophages collected from aged + PF-04418948-treated versus aged + vehicle-treated mice. Red dots indicate genes that are absolute-value[log₂(FC)] ≥ 1.5 and FDR < 0.05 by t-test with Benjamini–Hochberg correction. d, Top 10 signalling pathways from the Reactome pathway database for FDR < 0.05 genes comparing aged +veh versus young + v eh mice (top) and aged + PF-04418948 versus aged + veh mice (bottom). e, Hierarchical clustering of top differentially regulated chemokine and cytokines transcripts (FDR < 0.05) demonstrates that PF-04418948 treatment shifts expression towards young macrophage levels. f, Nanostring analysis of significantly regulated genes (FDR < 0.05) demonstrates differential expression of bioenergetic transcripts in peritoneal macrophages isolated from young (3–4 months) and aged (20–22 months) mice with or without PF-04418948 (2.5 mg/kg/d for 6 weeks). Aged peritoneal macrophages exhibit suppressed expression of genes that encode critical glycolytic enzymes, including the rate-limiting enzyme phosphofructokinase-1 (PFK-1) as well as the rate-setting TCA cycle enzyme, citrate synthase. Peripheral myeloid EP2 inhibition with PF-04418948 corrects the age-associated suppression of myeloid glycolytic and TCA cycle gene expression.