Figure 6. Another line of BRASTO mice that show higher Sirt1 expression through the hypothalamus exhibit the complete lack of life span extension, beneficial physiological phenotypes, and activation of the DMH and LH.

(A) Levels of Sirt1 mRNA in the Arc, VMH, DMH and LH of line 1 (left) and line 10 (right) BRASTO mice. Relative expression levels were calculated as the ratio of Sirt1 mRNA in BRASTO mice vs wild-type control mice. (*p<0.05, **p<0.01 by one-way ANOVA with Tukey-Kramer post hoc test, n=3 mice for each genotype). (B) mRNA expression levels of cFos in the Arc, VMH, DMH, and LH at 9pm. Results are shown as mean values ± S.E. (*p<0.05 by Student’s t-test, n=4–6 mice for each genotype). mRNA expression levels in each hypothalamic nucleus were normalized to that in the WT Arc. (C) Kaplan-Meier curves of line 1 BRASTO (Tg) and wild-type control (WT) mice in females (top left), males (top right) and combined sex (bottom left). P values were calculated by log-rank test. (D) Identified causes of death in aged line 1 BRASTO and wild-type control mice. (E and F) Wheel-running activity (E) and rectal body temperature (F) at 20 months of age. Results are shown as mean values ± S.E. (n=6–8 mice for each genotype). Shaded area represents the dark time. (G) mRNA expression levels of Pgcl α, Idh3 α, and Adrb2 in the soleus muscle of aged line 1 BRASTO mice and wild-type control mice at 9pm. Results are shown as mean values ± S.E. (n=3 mice for each genotype). See also Figure S6.