Raschenberger Julia, Kollerits Barbara, Titze Stephanie, Köttgen Anna, Bärthlein Barbara, Ekici Arif B, Forer Lukas, Schönherr Sebastian, Weissensteiner Hansi, Haun Margot, Wanner Christoph, Eckardt Kai-Uwe, Kronenberg Florian
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany.
Exp Gerontol. 2015 Dec;72:162-6. doi: 10.1016/j.exger.2015.09.019. Epub 2015 Sep 28.
Telomere length is considered as a biological marker for aging. It is expected that telomeres shorten with age and with conditions associated with oxidative stress and inflammation. Both are present in patients with chronic kidney disease (CKD) who have a very high cardiovascular risk. We investigated whether CKD duration is associated with relative telomere length (RTL) in 4802 patients from the German Chronic Kidney Disease (GCKD) study. We measured RTL in each sample in quadruplicates using a quantitative polymerase chain reaction (qPCR). We observed a U-shaped association of RTL with CKD duration: the longest RTL was found in those 339 patients who reported the shortest disease duration (<6 months) and shorter RTL in 2108 patients with duration between 6 months and less than 5 years. Most importantly, those 2331 patients who reported a CKD duration of 5 years and more had significantly longer RTL compared to those with intermediate CKD duration (6 months to less than 5 years): mean 0.954, 95%CI 0.946-0.961 versus 0.937, 95%CI 0.929-0.944, p=0.002). Due to the cross-sectional nature of the study these surprising results have to be considered with caution and as hypothesis-generating. Whether the longer RTL in patients with long-lasting disease is caused by an activation of telomerase to counteract the shortening of RTL due to oxidative stress and inflammation or whether they are caused by a survival bias needs to be investigated in longitudinal studies. Our data are in support of a higher plasticity of shortening and elongations of RTL as until recently anticipated.
端粒长度被视为衰老的生物学标志物。预计端粒会随着年龄增长以及与氧化应激和炎症相关的状况而缩短。这两种情况在心血管风险极高的慢性肾脏病（CKD）患者中均存在。我们在来自德国慢性肾脏病（GCKD）研究的4802名患者中，调查了CKD病程是否与相对端粒长度（RTL）相关。我们使用定量聚合酶链反应（qPCR）对每个样本进行四次重复测量RTL。我们观察到RTL与CKD病程呈U形关联：在报告病程最短（<6个月）的339名患者中发现RTL最长，而在病程介于6个月至不到5年之间的2108名患者中RTL较短。最重要的是，与CKD病程处于中间阶段（6个月至不到5年）的患者相比，报告CKD病程为5年及以上的2331名患者RTL显著更长：平均值分别为0.954，95%置信区间0.946 - 0.961与0.937，95%置信区间0.929 - 0.944，p = 0.002）。由于该研究的横断面性质，这些令人惊讶的结果必须谨慎看待，并仅作为假设提出。长期患病患者中较长的RTL是由端粒酶激活以抵消由于氧化应激和炎症导致的RTL缩短引起的，还是由生存偏差导致的，需要在纵向研究中进行调查。我们的数据支持RTL缩短和延长具有更高可塑性的观点，这与直到最近的预期一致。
