Opstad Trine Baur, Alexander Jan, Aaseth Jan, Larsson Anders, Seljeflot Ingebjørg, Alehagen Urban
Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, P.O. Box 4950, Nydalen, N-0424 Oslo, Norway.
Faculty of Medicine, University of Oslo, N-0370 Oslo, Norway.
Antioxidants (Basel). 2023 Mar 21;12(3):759. doi: 10.3390/antiox12030759.
: Selenium and coenzyme Q (SeQ) possess antioxidant and anti-inflammatory properties, potentially mediated via Sirtuin1 (SIRT1). We aimed to investigate the influence of a SeQ intervention on SIRT1 concentration, with potential interactions with microRNAs. : In this sub-study of a prospective double-blind placebo-controlled clinical trial, healthy subjects (mean age 76 years) were randomized to receive an active treatment ( = 165, combined 200 µg/day of Se and 200 mg/day of Q) or a placebo ( = 161). SIRT1 concentration and microRNAs were measured with ELISA and PCR, respectively. : After four years, SIRT1 concentration was increased in the active treatment group, with mean (SD) ng/mL of 469 (436) vs. 252 (162), < 0.001, and decreased in the placebo group, 190 (186) vs. 269 (172), = 0.002, and the differences between the groups were significant ( = 0.006, adjusted). Those who suffered CV death during a 10-year follow-up ( = 25 and = 52 in the active treatment and placebo groups, respectively) had significantly lower baseline SIRT1 concentrations compared to the survivors ( < 0.001). MiR-130a-3p was significantly downregulated during the intervention and correlated inversely with SIRT1 at baseline (r = -0.466, = 0.007). : The increased SIRT1 concentration after the SeQ intervention associated with reduced CV mortality, partly mediated via miR-1303a-3p, suggests that SIRT1 is an additional mediator of the intervention, preventing vascular ageing.
硒和辅酶Q(SeQ)具有抗氧化和抗炎特性,可能通过沉默调节蛋白1(SIRT1)介导。我们旨在研究SeQ干预对SIRT1浓度的影响,以及与微小RNA的潜在相互作用。
在这项前瞻性双盲安慰剂对照临床试验的子研究中,健康受试者(平均年龄76岁)被随机分为接受活性治疗组(n = 165,联合补充200μg/天的硒和200mg/天的辅酶Q)或安慰剂组(n = 161)。分别采用酶联免疫吸附测定法(ELISA)和聚合酶链反应(PCR)检测SIRT1浓度和微小RNA。
四年后,活性治疗组的SIRT1浓度升高,平均(标准差)为469(436)ng/mL,而安慰剂组为252(162)ng/mL,P < 0.001;安慰剂组的SIRT1浓度降低,为190(186)ng/mL,而之前为269(172)ng/mL,P = 0.002,两组之间的差异具有统计学意义(P = 0.006,校正后)。在10年随访期间发生心血管死亡的患者(活性治疗组和安慰剂组分别为25例和52例),其基线SIRT1浓度显著低于幸存者(P < 0.001)。在干预期间,miR-130a-3p显著下调,且在基线时与SIRT1呈负相关(r = -0.466,P = 0.007)。
SeQ干预后SIRT1浓度升高与心血管死亡率降低相关,部分通过miR-1303a-3p介导,这表明SIRT1是该干预的另一种介导因子,可预防血管衰老。