(A) Male shFxn mice treated with NAD+ precursors have significantly longer survival compared with nontreated mice. (B) NAD+ precursors significantly reduce LV posterior wall thickness at 16–18 weeks after doxycycline. (C) shFxn mice have increased heart weight relative to body weight at 16–18 weeks. (D and E) LV systolic and diastolic volumes and EF after 16–18 weeks measured by echocardiography. (F) Mitochondrial complex I respiration is modestly decreased in 16-week shFxn hearts. (G) Masson’s trichrome blue staining of LV section. Staining and quantification shows shFxn mice have fibrosis in hearts that is not reduced by treatment. Scale bar: 50 μM. A, pairwise Mantel-Cox test for survival vs. untreated, n = 10–11; B, D, and F, n = 4–12, 2-way ANOVA; C, E, and G, n = 4–12, 1-way ANOVA (*P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001).