Franny Jongbloed

215 8 BENEFICIAL EFFECTS OF A PREOPERATIVE DIET eIF2 reduces global translation, allowing cells to switch from growth to maintenance and inducing stress resistance 23 . These similarities highlight the evolutionary conservation of the response to DR, which is already present in humans after five days of CCPR. In addition, a trend towards inhibition of the immune response was seen. However, this did not reach statistical significance, presumably due to the small sample size and the heterogeneity of the human tissue. Other studies using DR in heart, skeletal muscle and liver tissue in animal models showed similar inhibition of cell cycle regulation and immune system signaling as well as an upregulation of stress response pathways, including the NRF2 pathway 24-27 . Transcriptome profiles of aged rat kidneys revealed an opposite image of our results induced by CCPR, such as the upregulation of immune pathways, including cytokine and T-cell signaling as well as NF-kB activation 28 , and are in agreement with our current results as long term diet restriction delays aging 2 . Recently, the transcription factor Myc was found as an important signaling molecule activated by protein restriction in Drosophila , potentiating innate immunity and increasing stress resistance 29 . We found MYC as one of the highest activated transcription factors following CCPR. Since pharmacological overexpression of Myc mimicked the effect of DR, MYC might well be a target to develop a dietary restriction mimetic 29 . No transcriptome analysis studies have been performed in human kidneys following DR. However, several reports on transcriptome profiling in human kidneys after transplantation were published recently. One of those performed gene expression analysis on biopsies three months after transplantation and identified 13 genes of interest that were correlated to worse allograft outcome at 12-months post-transplantation. Ankyrin repeat and SOCS Box containing 15 ( ASB15 ), was significantly decreased in their analysis and this downregulation was associated with worse kidney function at 12 months 30 . This gene was upregulated in the CCPR diet group in our unbiased profiling and might have a potential role in the protection against acute and chronic rejection 30 . Asb15 was discovered in 2002 as a member of the suppressor of cytokine box superfamily (SOCS) and is expressed mainly in the heart and kidney 31 . Not much is known about the function of the gene. The SOCS family, however, has been identified as a regulator of protein turnover and protein degradation, especially degradation of cytokines 32 . Another study, examining the link between interstitial fibrosis and gene expression profiles at 12 months after transplantation, revealed no similarities with our results 33 but found a relationship between increased serum levels of RBP and worse creatinine clearance. We showed that RBP levels decrease due to the diet, and it is worth looking into the functional role of RBP in relation to renal outcome 33 . Taken together, our transcriptome analysis shows hints towards increased stress resistance and possible downregulation of the immune response by DR. In addition, ASB15 revealed to be a gene of interest to investigate in future studies.