Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria.
Obes Surg. 2018 Sep;28(9):2804-2810. doi: 10.1007/s11695-018-3247-3.
Obesity is considered to be a major comorbidity. Obese patients suffer from an increased proinflammatory state associated with a premature aging phenotype including increased secretion of senescence-associated secretory proteins (SASP) and reduced telomere length. Micro-ribonucleic acids (miRNAs) are non-coding RNA molecules that could modify the post-transcriptional process. Several studies have reported associations between miRNAs and metabolic unhealthy conditions.
To determine if bariatric surgery and the resulting weight loss could reverse the premature aging phenotype.
We enrolled 58 morbidly obese patients undergoing bariatric surgery. Markers of premature aging including the SASP IL-6, CRP and PAI-1, 7 miRNAs, as well as telomere length and telomere oxidation in mononuclear cells were evaluated.
Patients showed a significant drop of body mass index (BMI; 43.98 ± 3.5 versus 28.02 ± 4.1, p < 0.001). We observed a significant reduction in SASP including a reduction of 55% of plasma IL-6 levels (p = 0 < 0.001), 83% of CRP levels (p = 0.001) and 15% of plasma PAI-1 levels (p < 0.001). Telomere length doubled in the patient cohort (p < 0.001) and was accompanied by a reduction in the telomere oxidation index by 70% (p < 0.001). Telomere length was inversely correlated with telomere oxidation. The aging-associated miRNA miR10a_5p was upregulated significantly (p = 0.039), while the other tested miRNAs showed no difference.
Our data indicate a significant reduction of the proinflammatory SASP after bariatric surgery. We observed an increase in telomere length and reduced oxidative stress at telomeres. miR10a_5p which is downregulated during aging was upregulated after surgery. Overall, bariatric surgery ameliorated the premature aging phenotype.
肥胖被认为是一种主要的合并症。肥胖患者患有与衰老表型相关的促炎状态增加，包括衰老相关分泌表型（SASP）的增加和端粒长度的减少。微小核糖核酸（miRNA）是一种非编码 RNA 分子，可以修饰转录后过程。一些研究报告了 miRNA 与代谢不健康状况之间的关联。
确定减重手术及其导致的体重减轻是否可以逆转衰老表型。
我们招募了 58 名接受减重手术的病态肥胖患者。评估了衰老的早期标志物，包括单核细胞中的 SASP IL-6、CRP 和 PAI-1、7 种 miRNA 以及端粒长度和端粒氧化。
患者的体重指数（BMI）显著下降（43.98±3.5 与 28.02±4.1，p<0.001）。我们观察到 SASP 显著减少，包括血浆 IL-6 水平降低 55%（p<0.001）、CRP 水平降低 83%（p=0.001）和 PAI-1 水平降低 15%（p<0.001）。患者组的端粒长度增加了一倍（p<0.001），同时端粒氧化指数降低了 70%（p<0.001）。端粒长度与端粒氧化呈负相关。与衰老相关的 miRNA miR10a_5p 显著上调（p=0.039），而其他测试的 miRNA 没有差异。
我们的数据表明，减重手术后 SASP 的促炎作用显著降低。我们观察到端粒长度增加，端粒氧化应激减少。miR10a_5p 在衰老过程中下调，手术后上调。总体而言，减重手术改善了衰老表型。
