Extended Data Fig. 5: TREM1 deficiency restores youthful metabolism in aged macrophages.
a PCA of metabolites from young (2 mo) WT and Trem1-/- peritoneal MΦ (n = 3 male mice per group). b PCA of significantly regulated metabolites from primary peritoneal MΦ isolated from young WT (2 mo), aged WT (25 mo) and aged Trem1-/- (25 mo) male mice. n = 3–5 male mice per group. c Volcano plot comparing aged WT vs young WT (left) and aged Trem1-/- vs aged WT (right) peritoneal MΦ with Log2 fold change (FC) and -Log10(P) values of metabolites. Significantly regulated metabolites with -log10(P) > 2 and log2 fold change > 1 are shown in blue. d KEGG metabolic pathway enrichment analysis of differentially regulated metabolites between aged WT and young WT macrophages and between aged Trem1-/- vs aged WT MΦ. X-axis shows -Log10(q) value. No pathways were significant following FDR correction for the comparison of aged Trem1-/- vs young WT. Pathway analysis was performed using MetaboAnalyst 5.0; n = 3–5 male mice per group. e Total ion count of Ribose-5P, the precursor of purines and pyrimidines and total ion counts for nucleobases and derivatives, ribo-nucleosides, deoxynucleosides, and nucleoside monophosphates. Data are analyzed by one-way ANOVA with Tukey’s multiple comparisons (n = 3–5 male mice per group). Abbreviations: AMP: adenosine monophosphate, GMP: guanosine monophosphate, UMP: uridine monophosphate, CMP cytidine monophosphate, IMP: inosine monophosphate. n = 3–5 male mice per group as shown. f Transcription factor (TF) enrichment analysis revealing TFs enriched for differentially expressed metabolite enzymes. g FKPM of NRF2. ANOVA followed by Tukey’s multiple comparison (n = 3–4 male mice per group as shown). h FKPM of the 3 pyruvate dehydrogenase complex (PDH) subunits: pyruvate dehydrogenase (PDHA1), dihydrolipoyl transacetylase (DLAT) and dihydrolipoyl dehydrogenase (DLD); ANOVA followed by Tukey’s multiple comparison (n = 3–4 male mice per group as shown).
