(A) Volcano plot indicating upregulated and significantly downregulated genes in heart tissue of shFxn male mice at 16 weeks after doxycycline. Red are significantly upregulated or downregulated (Padj ≤ 0.05, FDR-adjusted Wald test). (B) Fxn is not recovered by precursor treatment (mean, lower, upper bound; WT: 1.085, 0.763, 1.402; shFxn: 0.019, 0.006, 0.025; NR: 0.021, 0.016, 0.030; NMN: 0.017, 0.012, 0.020), Hmox1 is highly induced in shFxn mice (WT: 151.6, 115, 196; shFxn: 2,303, 1,773, 2,909; NR: 1,906, 387, 2,649; NMN: 1,677, 581, 3,063). (C) Heatmap of all transcripts demonstrating minor transcriptional changes with treatment. (D) Upregulated and downregulated reactome terms in shFxn mice. (E) Subset of genes that are modified by NR and NMN.