Effects of long term weight loss on cellular aging reflected by leukocyte telomere length

The prevalence of overweight and obesity is increasing worldwide. Obesity is associated with diabetes mellitus, coronary heart disease, certain forms of cancer, and sleep-breathing disorders. Bariatric surgery is capable to induce long-term weight loss and ameliorate most obesity-associated risk factors. The aim of this prospective study is to investigate the association between obesity and biological aging expressed by leukocyte telomere length. Human leukocyte telomere length has been proposed to be a biomarker for aging. It is associated with age-related disorders, predominantly atherosclerosis. Individuals with higher total and abdominal adiposity have lower leukocyte telomere length, suggesting obesity may hasten the aging process. Therefore, data from patients who participated in a previous study at our institution investigating the effects of weight loss on glucose and lipid metabolism and atherosclerosis in the years 1998 to 2005 will be contacted and follow up examinations will be performed. The proposed research project will bring new insights into recently published evidence of reduced long-term morbidity and mortality after bariatric surgery induced weight loss.

The present project revealed that telomere-length in leukocytes was maintained or even elongated following pronounced weight loss due to surgical treatment. Telomeres describe a specific structure that covers the edge of the cells genetic material, hereby protecting it from attrition and structural damage. If a cell would not have telomeres covering the edge of the genetic material, it would be at risk to be shortened each time the cell was about to divide, which in turn would trigger cell death. Telomeres get shortened instead of genetic material, allowing the cell to divide as long as telomere length is sufficient. As a result, the longer the telomere length, the longer is the survival of the cell. Former studies have shown that telomeres were shorter on the presence of certain risk factors like overweight, smoking, high blood lipids, elevated blood glucose and malignant disease. The present scientific project investigated patients who had a surgical intervention in order to lose body weight (a so called bariatric surgery). We investigated a total of 142 persons prior to and 10 years after the surgical intervention. Medical data comprised telomere length, body weight, body composition, blood lipids, and blood glucose concentrations. It was found that telomere attrition was faster in the presence of elevated blood glucose concentrations and higher blood lipids. As a next step, we measured telomere length in 142 age and gender matched inhabitants of the healthy general population over a time period of 10 years. These participants were non obese and deemed healthy from a clinical point of view. It was found that telomere attrition was faster in the healthy general population compared to patients who had bariatric surgery. In these patients, telomere length was not only found to abbreviate to a lesser extend but also to even elongate, compared to healthy subjects. However, telomere attrition was independent of the actual amount of body weight lost due to the bariatric surgery. It was found that the improvements in metabolism and the reduction in metabolic risk factors (blood lipids, blood glucose) were the determining factor, which maintained or even elongated telomere length. This underlines the importance of a healthy lifestyle in order to maintain cell survival.