Franny Jongbloed

33 2 FASTING PROTECTS AGED-OVERWEIGHT MICE The qRT-PCR data confirmed the upregulation of Pparα , Gst2 , Cyp4a14 with fold increases of 2.5, 8.0 and 106 respectively in young and 2.2, 3.4 and 147, respectively in aged kidneys. The downregulation of Sc4mol was also validated with qRT-PCR and showed a significant 1.77-fold decrease in young and 1.72-fold in aged kidneys (Table 3). Table 2. Top 15 canonical pathways overlapping in aged and young mice in response to fasting compared with ad libitum Canonical Pathways OVERLAP P- value Genes Ratio LPS/IL-1 Mediated Inhibition of RXR Function 7.85 E -07 18/245 (7.3%) LXR/RXR Activation 1.27 E -06 13/139 (9.4%) Fatty Acid β-oxidation I 2.00 E -06 7/45 (15.6%) Superpathway of Cholesterol Biosynthesis 2.85 E -05 6/87 (6.9%) Dopamine Degradation 1.10 E -04 5/38 (13.2%) Androgen Biosynthesis 1.50 E -04 4/26 (15.4%) Alanine Degradation III/Biosynthesis II 4.22 E -04 2/6 (33.3%) Retinoate Biosynthesis I 4.57 E -04 5/37 (13.5%) Stereate Biosynthesis I (Animals) 7.01 E -04 5/49 (10.2%) NRF2-mediated Oxidative Stress Response 1.29 E -03 11/195 (5.6%) Serotonin Degradation 1.56 E -03 6/78 (7.8%) TR/RXR Activation 1.84 E -03 7/109 (6.4%) FXR/RXR Activation 1.97 E -03 7/110 (6.4%) Cholesterol Biosynthesis I 2.12 E -03 3/40 (7.5%) Bile Acid Biosynthesis, Neutral Pathway 2.12 E -03 3/58 (5.2%) Canonical pathways overlapping in aged and young mice after 3-day fasting with their corresponding geometric mean P- value and the percentage of regulated genes. DISCUSSION With publications dating back 80 years, DR is one of the most extensively investigated interventions in biology 18,19 . Long-term DR leads to prolongation of health- and lifespan in many animal species 11 as well as an increase in acute stress resistance 20 . Induction of organ ischemia is a widely used model to examine the effects of DR, since it has been shown to increase the resistance against ischemic injury in organs like heart and brain 21,22 .