Franny Jongbloed

34 CHAPTER 2 Previous research done in one of our laboratories showed that applying short periods of DR (two and four weeks 30% DR) as well as three days of fasting, conveyed strong protection against morbidity and mortality induced by IRI in the kidney as well as decreased morbidity and improved liver function in a non-lethal liver IRI model 9,23,24 . Table 3. Validation via qRT-PCR of four genes found to be significant in the array analysis Gene Aged (Affy) Aged - qPCR Young (Affy) Young - qPCR Pparα 2.53/ 3.00 E -09 2.5/6.83 E -07 2.74/1.45 E -05 2.2/0.0005 Gsta2 5.52/2.45 E -08 8.0/3.12 E -05 8.72/3.73 E -05 3.4/1.52 E -05 Cyp4a14 344.47/4.11 E -09 106/6.16 E -06 126.72/9.85 E -07 147/0.0003 Sc4mol -2.64/5.16 E -07 -1.77/0.005 -4.98/1.69 E -06 -1.72/0.007 Fold ratios and corresponding p- values obtained via microarray analysis (Affy) and qRT-PCR (qPCR) of four genes found to be significant in the performed array analysis. A drawback of the majority of reports is that for practical reasons the same animal model was utilized, namely healthy young (8-12 weeks) male mice of one genetic background (C57BL/6). These mice poorly represent the heterogeneous human population. In particular, this is valid for ECD whom are older and usually overweight. In this study, we showed that preoperative fasting strongly protects both male and female aged-overweight mice against renal IRI, with a significantly reduced mortality after IRI and better preserved kidney function and morphology. Compared to young mice, the recovery of body weight in fasted aged mice takes longer, probably at least in part due to their greater fat reserve and therefore reduced need to restore body weight in order to survive. Previously we observed that fasted young mice started eating shortly after surgery and showed a rapid increase in body weight. We showed that postoperative food intake and associated weight gain did not contribute to the observed protection 9 . The prolonged modest postoperative weight loss in the fasted aged mice provides additional evidence that postoperative feeding is not involved. In addition, the relative body weight loss in aged mice was less than in the young cohort, leaving these mice with more remaining body fat after fasting and IRI. These results indicate that weight loss and reduction of body fat coincide with but do not contribute to the protection against IRI induced by preoperative deprivation of food. We compared and analyzed the overlap of gene expression data of young and aged mice via microarray analysis, narrowing down genes and pathways possibly involved in the effect of fasting. We found a striking corresponding directionality in overlapping genes of both groups with the changes being more pronounced and more often significant in the young group. Possibly, aged organs and tissues are not able to mount a more vigorous response as