Franny Jongbloed

29 2 FASTING PROTECTS AGED-OVERWEIGHT MICE from young mice. A total of 2,408 probe sets were found to be significantly differentially regulated in fasted compared with ad libitum fed young mice with 1,189 upregulated and 1,219 downregulated probe sets (Figure 5A). Figure 3. Histopathological analysis of kidneys after renal ischemia-reperfusion injury. Mice sacrificed at the end of the experiment showed significantly less acute tubular necrosis (A) and significantly more tubular epithelial regeneration (B) . Divided by intervention, both male and female fasted mice also showed less necrosis (C) and more regeneration (D) . Fasted male mice sacrificed at day 7 showed similar pathology scores as the fasted mice at day 28 (mice indicated by the red symbols). * = significance ( P< 0.05) compared to the group ‘Found dead’, ** = compared to the group ‘Moribund’, *** = compared to ad libitum fed males, **** = compared to ad libitum fed females. The Venn diagram in Figure 5A shows that most probe sets (70%) found in agedmice overlap with the probe sets found in young mice. Young mice show an almost three-fold increase of significantly regulated genes indicative of a stronger, more extensive response to fasting in young compared to aged mice. To verify whether gene expression changes followed the same directionality, the fold expression changes of all significant probe sets (FDR ≤ 5%) in

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