Figure 4. NR ameliorates deficits in mNKO mitochondrial function and fiber morphology.
A, Treadmill running performance of 7-month-old mice provided with unsupplemented drinking water (Veh) or NR-supplemented drinking water for 6 weeks and
B, Concentration of blood lactate at baseline and at the point of exercise exhaustion (n=4–8).
C, Distribution and descriptive statistics of minimum Feret diameters of EDL fibers. Inset: proportion of centrally nucleated fibers (CNF). At least 2.0×103 fibers from 3 individuals per group were considered.
D, Respiratory capacity of muscle mitochondria provided with excess palmitoyl carnitine or
E, Excess pyruvate (n=4–6, significant changes relative to mNKO Veh).
F, Intramuscular ATP content (n=4–7) in quadriceps muscle following NR treatment.
G, Intramuscular NAD content (n=4–7) and
H, Mitochondrial NAD
I, Relationship between oxygen consumption and NAD content of mitochondria isolated from skeletal muscle (n=4–6). The line indicates a rectangular hyperbolic least squares regression and associated correlation coefficient.
J, Relationship between complex I-dependent respiration and basal NAD content of mitochondria isolated from C2C12 myotubes treated for 24 hours with 10 nM FK866 and 0–300 µM NR. The line indicates a rectangular hyperbolic least squares regression and associated correlation coefficient. Error bars represented SEM. Significance was determined by one-way ANOVA with Tukey’s post-hoc test (ns, not significant, *p<0.05,***p<0.001). Mice were female aged 7 months at sacrifice.