Franny Jongbloed

248 CHAPTER 9 by markers such as Cyclin D1 41 . Although detrimental effects of fasting on the effects of chemotherapy or on the main tumors have not been reported, implications have been made about the additional beneficial effects of DR on tumorigenesis and cancer treatment 20 . In our data, on a transcriptional level the changes induced by fasting in healthy liver tissue were not present in tumor tissue. The transcriptomic profiles of the tumor tissue were very heterogeneous, and therefore our analyses could not detect specific changes induced by fasting in tumor tissue treated with irinotecan. These data support the differential stress sensitization theory, which states that beneficial alterations in normal cells due to nutrient deprivation protects them against chemotherapy induced toxicity whilst these changes do not occur in cancer cells 42 . The search for a clinically applicable dietary intervention The misbalance of increasing body of evidence showing the benefits of both long-term and short-term DR in various animal models, including non-human primates, and only few clinical studies concerning DR is indicative for the problems associated with translation of DR to a clinical setting 43,44 . Multiple reasons for the absence of clinical implementation have been given over time 45 . Foremost, the metabolic rate of mice is a multitude of that of humans which suggests prolonged periods of DR in humans. The difficulty for humans to comply to such periods of DR is intense, even though a small group of long-term DR- believers has been able to restrict themselves of 30% calories for many years now and do show signs of improved metabolic profile. Moreover, the generally held belief that the advantages of normal to high food intake prior to surgery is in conflict with the principle of preoperative nutrient restriction 45 . Therefore, obtaining more evidence of the safety, feasibility and effects of a dietary intervention in a clinical setting was warranted to change the current preoperative nutritional care in patients. To start with, a model that is opposite to nutrient deprivation might be of additional value in order to fully understand the effects of DR and the way it affects surgical outcome. Therefore, in chapter 6 , the link between inflammation, aging and surgery was investigated by examining markers of aging and the immune system in patients with morbid obesity undergoing bariatric surgery. Morbid obesity is known to negatively affect mortality and increases the risk of age-associated diseases, including diabetes mellitus, cardiovascular disease and cancer 46 . This link is thought to be caused by the chronic subclinical inflammatory state as seen in morbidly obese patients, which is caused by an over activation of the immune system as induced by white adipose tissue 47 . This inflammation has a direct effect on the immune system and is thought to cause premature aging of the immune system, a phenomenon called ‘inflammaging’ 48 . This is possibly even worse in patients who are metabolically compromised by the presence of the metabolic syndrome, which might be