Pusceddu Irene, Herrmann Wolfgang, Kleber Marcus E, Scharnagl Hubert, März Winfried, Herrmann Markus
Department of Clinical Pathology, Hospital of Bolzano, Bolzano, Italy.
Department of Clinical Chemistry, University of Saarland, Homburg, Germany.
Aging (Albany NY). 2019 Sep 6;11(17):7083-7097. doi: 10.18632/aging.102238.
Vitamin B12 (B12) deficiency and excess are associated with increased risk of age-related-diseases and mortality. It has been suggested that high- and low-B12 concentrations link to increased mortality through accelerated genomic aging and inflammation. Evidence to support this is limited.
B12 was associated with all-cause-mortality, RTL and hsCRP in a non-linear fashion. The association between B12 and mortality was not independent, as it lost significance after adjustment for potential confounders. In the lowest-(LB12) and highest-(HB12) quartiles of B12 mortality was higher than in the mid-range (HR:LB12:1.23;CI95%:1.06-1.43; HR:HB12:1.24;CI95%:1.06-1.44). We divided subjects with LB12 in quartiles of their RTL. Those with the longest-telomeres had a lower mortality-rate (HR:0.57;95%CI:0.39-0.83) and lower homocysteine than those with the shortest-telomeres. Amongst subjects with HB12, those with long-telomeres also had a lower mortality than those with short-telomeres (HR:0.40;95%CI:0.27-0.59). IL-6 and hsCRP concentrations were low in HB12LT but were high in HB12ST.
B12, homocysteine, telomere length (RTL), interleukin-6 (IL-6) and high-sensitive-C-reactive-protein (hsCRP) were measured in 2970 participants of the LURIC study.
Mortality, stratified according to B12 and RTL, seems to be driven by different mechanisms. In LB12 and HB12 subjects, mortality and accelerated telomere shortening might be driven by homocysteine and inflammation, respectively.
维生素B12(B12)缺乏与过量均与年龄相关疾病及死亡风险增加有关。有人提出,高、低B12浓度通过加速基因组衰老和炎症反应导致死亡率上升。但支持此观点的证据有限。
B12与全因死亡率、端粒长度(RTL)及高敏C反应蛋白(hsCRP)呈非线性相关。B12与死亡率之间的关联并非独立存在,在对潜在混杂因素进行校正后其显著性消失。在B12最低四分位数(LB12)组和最高四分位数(HB12)组中,死亡率高于中间范围组(风险比:LB12组为1.23;95%置信区间:1.06 - 1.43;风险比:HB12组为1.24;95%置信区间:1.06 - 1.44)。我们将LB12组受试者按其RTL分为四分位数。端粒最长者死亡率较低(风险比:0.57;95%置信区间:0.39 - 0.83),且同型半胱氨酸水平低于端粒最短者。在HB12组受试者中,端粒长者死亡率也低于端粒短者(风险比:0.40;95%置信区间:0.27 - 0.59)。HB12组中端粒长者IL - 6和hsCRP浓度较低,而端粒短者则较高。
对LURIC研究中的2970名参与者测量了B12、同型半胱氨酸、端粒长度(RTL)、白细胞介素 - 6(IL - 6)和高敏C反应蛋白(hsCRP)。
根据B12和RTL分层的死亡率似乎由不同机制驱动。在LB12和HB12组受试者中,死亡率和端粒加速缩短可能分别由同型半胱氨酸和炎症反应所致。