Franny Jongbloed

30 CHAPTER 2 young or aged mice were plotted against each other (Figure 5B). The majority of these probe sets (85%) had similar directional changes in kidneys of young and aged mice, although the fold changes of the aged kidneys were generally lower compared to young. (A) (B) (C) (D) (E) Figure 4. Representative images of HE stained kidney sections with acute tubular necrosis or tubular epithelial regeneration. (A) Multifocal severe acute tubular necrosis with typical diluted tubules, flattened epithelial lining and granular casts inside the tubules (arrows) in ad libitum fed male mouse four days after 37 minutes of IRI. (B) On day 7, male fasted mice already show a high degree of regeneration (arrows) with minimal necrosis (stars). (C) Multifocal tubular regeneration as shown by mitosis bodies along the epithelial line (arrows) in a fasted male mouse 28 days after 37 minutes of IRI. (D) Multifocal severe acute tubular necrosis in ad libitum fed female mouse four days after 60 minutes of IRI. (E) Multifocal tubular regeneration in a fasted female mouse 28 days after 60 minutes of IRI. To determine the effect on a biological level, functional annotation and pathway overrepresentation analyses of probe sets with FDR ≤ 5% and FC ≥ 1.5, were performed with Ingenuity software. The top up- and downregulated genes (FC ≥ 5) with corresponding P- values resulting fromthe functional annotationareprovidedas supplementary tablesbyage group (Table S1-S4). Pathway analysis in aged mice resulted in the highest overrepresented pathways being LXR/RXR Activation , Cholesterol Biosynthesis and Fatty Acid β-Oxidation (Table 1). The most overrepresented pathways in young-lean male mice were Cholesterol