Fig. 4: Combined treatment with trametinib and rapamycin counteracts the age-related increase in brain glucose uptake.
Longitudinal 18F-FDG PET/CT measurements of age-related changes in differential glucose uptake in the female mouse brain. a–c, Images show differential regional glucose uptake across the mouse brain between 24-month-old and 12-month-old control (a), trametinib-treated (b) and rapamcin/trametinib-treated (c) female mice. Color code represents the P value for the indicated voxels in a paired Student’s t-test comparing 24-month-old to 12-month-old animals. Increase in glucose uptake is shown in red/yellow, decrease in blue color. d, Two-way ANOVA analysis highlights brain regions that showed a significant interaction between age and drug treatment in differential glucose uptake. A lighter green color indicates a higher significance in the two-way ANOVA analysis. e,f, Longitudional quantification of glucose uptake in whole brain, striatum, cerebellum and cortex at 12, 18 and 24 months of age in control (e), trametinib-treated (f) and rapamycin/trametinib-treated (g) mice. Glucose uptake significantly increased with age in striatum and cerebellum of control animals but not in combination-treated animals. Data are presented as mean ± s.e.m. h,i, Images show differential glucose uptake in the brain of 24-month-old trametinib versus control (h) and combination versus control (i) mice. j–m, Quantification of differential glucose uptake between 12-month-old and 24-month-old whole brain (j), striatum (k), cerebellum (l) and cortex (m). Decrease in glucose uptake is indicated in blue color. Age-related differences in glucose uptake between 12 months and 24 months were significantly lower in combination-treated animals compared to controls. A similar but milder effect was also observed in trametinib-treated animals, which was only significant in the cerebellum. Two-way ANOVA with Bonferroni post hoc test. Data are presented as mean with s.e.m. a–g and j–m, Numbers in brackets indicate the number of whole brains/brain regions analyzed per treatment and timepoint. M, months.
