5922A novel APJ ligand, ELABELA/Apela/Toddler, protects from pressure overload- and Angiotensin II-induced cardiac hypertrophy and fibrosis

Abstract

Reversal of premature aging markers after bariatric surgery Authors: Background: Obesity is considered to be a major risk factor in developing cardiac disease. In addition, obese patients suffer from a premature aging phenotype including increased secretion of senescence associated secretory proteins (SASP) and reduced telomere length compared to healthy controls. Purpose: The aim of our study was to determine, if bariatric surgery and the resulting weight loss could reverse the previously observed premature aging phenotype. Methods: We enrolled 76 patients undergoing bariatric surgery. Blood samples were taken before and 12 months after surgery. Markers of premature aging including the SASP IL6 and PAI?1 as well as telomere length and telomere oxidation were evaluated. Results: Overall, patients showed a significant drop of body mass index (44.5±4.2 before surgery versus 27.5±3.6 after surgery, p<0.001). In addition plasma levels for IL6 (3.1±2.4 pg/ml before versus 1.7±1.5 pg/ml after bariatric surgery, p<0.001) and PAI?1 (98.4±17.2 ng/ml before versus 83.8±27.1 ng/ml after bariatric surgery, p<0.001) were significantly reduced after surgery. Telomere length on average increased by 58% in the patient cohort (0.37±0.28 a.u. before versus 0.59±0.28 a.u. after bariatric surgery, p<0.001). The telomere increase was accompanied by a reduction in the telomere oxidation index (2.86±4.4 before versus 0.78±0.56 after bariatric surgery, p<0.001) indicating reduced oxidative stress for the telomeric region. This is further supported by an inverse correlation of telomere length with telomere oxidation at both time points (r=?0.376, p<0.001 pre surgery and r=?0.705, p<0.001 post surgery). Conclusion: Our data indicate a significant reduction of the SASP IL6 and PAI?1 in plasma 12 months after bariatric surgery. In addition we observed an increase in telomere length in this setting. However, given the reduction in oxidative stress at telomeric regions we speculate that the increased telomere length is not due to active elongation but due to reduced breakage caused by telomere oxidation. Overall, bariatric surgery ameliorated the premature aging phenotype of previously morbidly obese patients.