Franny Jongbloed

249 9 SUMMARY AND DISCUSSION partially reversed by bariatric surgery. We showed that obesity itself did not affect relative telomere length (RTL), however the presence of metabolic syndrome significantly decreased the RTL of CD4 + T-cells. This shortening of RTL was accompanied by an increase of fully maturated T cells, indicating that the complete T-cell compartment is affected by obesity. Bariatric surgery, which is de definitive solution for morbid obesity once all other options have failed, could partially forestall this effect 49 . At three and six months after surgery, the significant decrease of RTL seen prior to surgery was no longer present, indicating that the shortening was halted. However, RTL at 12 months postoperatively was similar to the length prior to surgery, suggesting bariatric surgery affects RTL only in the first phase after surgery. These data show that metabolically compromised morbidly obese patients show signs of accelerated immune aging, which gives important insight into the increased risk of morbidity and mortality of these patients. Therefore, the metabolic syndrome predisposes to accelerated T-cell aging and is temporarily reversed by obesity-reducing surgery. As it comes to DR, previously colleagues showed the feasibility and safety of a preoperative DR regimen in a clinical setting. A preoperative diet including three days of 30% DR followed by 24 hours of fasting was well adhered to by living kidney donors, and no preoperative, perioperative or postoperative complications due to the diet were seen 50 . However, the diet only induced marginal effects on postoperative outcome 51 . In chapter 2 we used an optimal model to study human aging and obesity and demonstrated that DR is applicable independent of age and body weight, although aging did result in a dampening of the transcriptomic response. In addition, we showed that both male and female genders are protected against IRI by DR. Chapter 4 pointed us towards the additional effects of protein restriction on IRI. With our extended knowledge of protein restriction and handling of such a diet by patients, in chapter 7 we developed a combined calorie and protein restricted diet to further investigate in a clinical setting. We showed the safety, feasibility and adherence to the diet in two surgical patient populations, namely living kidney donors and morbidly obese patients. A total of 71% of the donors and bariatric surgery patients complied to the restricted diet, which induced minor discomfort in about two-third of the patients. All discomforts, mainly gastro-intestinal changes, scored low on the visual analogue scale and quickly resolved after normal eating pattern was resumed. The patients that did withdraw early from the diet, reported discomfort as the main reason. Especially the morbidly obese patients awaiting bariatric surgery suffered from discomfort, possibly due to the increased prevalence of functional gastrointestinal disorders in obese patients 52 . Adherence to the diet could be objectively measured via metabolic parameters prealbumin (PAB) and retinol binding protein (RBP). Serum levels of both markers significantly decreased due to the restricted diet compared to the placebo diet and control group. Branched chain amino acids leucine and valine were both significantly decreased in the diet group, while no changes occurred in the placebo or control group. One patient in the control group showed no