(A–D) Mouse quadriceps sections of indicated genotypes were stained for hematoxylin and eosin and representative 30-week-old images are shown. Scale bars are 50 μm. (E) Quantification of the average minimum Feret's diameter of muscle fibers at ages indicated. *p < 0.05, **p < 0.005 (t-test). For 10 weeks, n = 3, 3, 4, and 3 per genotype, respectively. For 20 weeks, n = 4, 3, 5, and 5. For 30 weeks, n = 7, 5, 5, and 8. For 40 weeks, n = 2, 5, 4, and 3. More than 500 fibers were scored per animal. See also Figure 7—figure supplement 1. (F–I) Reduced NLK expression improves the defective NADH transferase activity pattern seen in BAC fxAR121+/− mouse muscle. Six littermate sets were compared and representative images at 30 weeks of age are shown. Scale bars are 200 μm. See also Figure 7—figure supplement 2. (J) Kaplan–Meier survival analysis shows a significant extension in the lifespan of BAC fxAR121+/− mice with a 50% reduction of NLK. p = 0.00107 (log rank test). n = 27, 27, 51, and 37 per genotype, respectively.