(A) Body weights of male (top) and female (bottom) shFxn mice following the initiation of doxycycline at 12–16 weeks of age (n = 4–7). (B) Survival curves for each sex after doxycycline (n = 4–7). (C) Ejection fraction recorded at 18 weeks after doxycycline and LV volumes at end systole and diastole (n = 2–7). (D) Systolic LV posterior wall measurements (n = 2–7). (E) Respirometry in isolated heart mitochondria from males (20 weeks after doxycycline) and females (26 weeks after doxycycline) (n = 2–7). (F) Heart tissue NAD+ (n = 2–7). (G) Heart mitochondrial NAD+ (n = 2–7). A and E, 2-way ANOVA; B, Mantel-Cox test for survival; C, D, F, and G, 1-way ANOVA (*P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001).