Franny Jongbloed

156 CHAPTER 6 T-cell aging is associated with attrition of telomeres, which can be easily measured in circulating T-cells via flowcytometry 22,35 . A relationship between obesity and telomere attrition in circulating leukocytes and T-cells has been previously been described, however the results are ambiguous 11,24,36,37 . One study also investigated the importance of MetS but could not find a deleterious role of MetS on telomere shortening in leukocytes 39 . In addition to obesity itself, we show that enhanced telomere attrition occurs when MetS as a comorbidity is present in morbidly obese patients, most notable in patients of ≤50 years. Differences in the methods used to measure telomere length might contribute to the discrepancies with other studies. Namely, the other groups used a quantitative PCR assay technique to measure relative telomere length and our flowcytometry assay might be more sensitive to pick up differences within a particular population of T-cells 36 . The hypothesis that bariatric surgery ameliorates attrition of telomeres in addition to resolving the obesity-associated diseases such as diabetes mellitus, has been investigated previously but results are inconclusive 36,37 . These studies are not directly comparable since the follow-up period after bariatric surgery differs between one and 10 years. Formichi et al. 37 showed a significant decline at three, six and 12 months postoperatively, while we showed a trend towards increase in RTL in the first three months postoperatively until a decline was seen only at 12 months postoperatively. This improvement induced earlier on after surgery is in line with the rapid weight loss and reversal of diabetes mellitus as seen after bariatric surgery 25 . As Formichi et al. mentioned, the decline in RTL could be induced by the acute catabolic state induced by bariatric surgery 37 . Further research and larger cohort studies are warranted in order to investigate whether RTL might be further restored after bariatric surgery and at which time point this might be visible. In addition to the effects on RTL, bariatric surgery also induced subtle changes in the T-cell differentiation state, a link that has not been investigated previously. Especially in the total obesity group a decrease in more matured T-cells was shown, while MetS revealed to be an independent factor for the decrease in CD4 + CD28null T-cells. These results underscore that bariatric surgery may restore the premature immunological T-cell aging seen in morbidly obese patients. Since the eligibility of bariatric surgery is still largely dependent on general indicators such as BMI, this study justifies the need for clarification of the criteria for bariatric surgery based on individual patient characteristics. Telomere attrition and T-cell differentiation status are influenced by various, mostly non- adjustable factors such as age and CMV-seroposivity 22 . While we show no differences in RTL due to these factors, we do demonstrate that CMV and age are both independent factors for enhanced T-cell differentiation status. These results were most prominent in the CD8 + T-cell population, which is in line with previous findings 34 . We also identified the effect of gender on RTL as well as T-cell differentiation, since the restoration of RTL