Figure 2

Improved metabolic homeostasis in CYB5R3-Tg mice. (a) Kaplan–Meier survival curve for CYB5R3-Tg (n=69) and Wt (n=64) male mice. Extension of 20% maximal lifespan in CYB5R3-Tg mice was significant (P=0.0088, two-tailed t-test). (b) Kaplan–Meier survival curves of male mice fed SD alone (n=14) or supplemented (n=16) with 2.7 mg THII per kg body weight. The arrow at 113 weeks indicates the age at which THII treatment was started. (c) Relative expression value of Cyb5r3 transcript assessed by microarray analysis of RNA isolated from the kidney, liver and skeletal muscle of TFII-fed mice versus control animals, n=4 per group. **P<0.01 and ***P<0.001. (d) Body weight profile over the lifespan. Data include all live animals at each time point. (e) Lean and fat percentages in mice were determined by nuclear magnetic resonance (NMR). (d,e) n=64–69 mice per group. (f) Lean-to-fat ratio. n=6–13 mice per group. (g) Protocol design. Male mice (18–23 weeks old) were fed SD (n=8 CYB5R3-Tg and n=15 Wt mice) or HFD (Supplementary Section) for 17 weeks. At the indicated time points (weeks), the following measures were performed: Ins/Glu, insulin and glucose determination; RR, rotarod; MC, metabolic cages; Sac, sacrifice of the animals. (h–n) The following analyses were carried out in mice after a 20-h fasting period: (h) serum triglycerides; (i) total serum cholesterol; (j) high-density lipoprotein (HDL) content; (k) low-density lipoprotein (LDL) content; (l) blood glucose levels; (m) serum insulin levels; and (n) HOMA-IR index. (h–k) n=5 per group; (l–n) n=7–12 per group. (o,p) Sixteen weeks after SD feeding, mice were placed into metabolic cages for the measure of (o) in vivo oxygen consumption and (p) respiratory exchange ratio (RER), n=4–6 per group. (q) Time to fall from an accelerating rotarod, n=7–15 per group. Data are represented as the mean±s.e.m. *P<0.05 compared with Wt mice.