Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden.
Norwegian Institute of Public Health, 0213 Oslo, Norway.
Cells. 2023 Jul 4;12(13):1773. doi: 10.3390/cells12131773.
Ageing is associated with cardiovascular disease (CVD). As no single biomarker reflects the full ageing process, we aimed to investigate five CVD- and age-related markers and the effects of selenium and coenzyme Q10 intervention to elucidate the mechanisms that may influence the course of ageing. This is a sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial that included 441 subjects low in selenium (mean age 77, 49% women). The active treatment group (n = 220) received 200 µg/day of selenium and 200 mg/day of coenzyme Q10, combined. Blood samples were collected at inclusion and after 48 months for measurements of the intercellular adhesion molecule (ICAM-1), adiponectin, leptin, stem cell factor (SCF) and osteoprotegerin (OPG), using ELISAs. Repeated measures of variance and ANCOVA evaluations were used to compare the two groups. In order to better understand and reduce the complexity of the relationship between the biomarkers and age, factor analyses and structural equation modelling (SEM) were performed, and a structural model is presented. Correlation analyses of biomarker values at inclusion in relation to age, and relevant markers related to inflammation, endothelial dysfunction and fibrosis, demonstrated the biomarkers' association with these pathological processes; however, only ICAM1 and adiponectin were directly correlated with age. SEM analyses showed, however, that the biomarkers ICAM-1, adiponectin, SCF and OPG, but not leptin, all had significant associations with age and formed two independent structural factors, both significantly related to age. While no difference was observed at inclusion, the biomarkers were differently changed in the active treatment and placebo groups (decreasing and increasing levels, respectively) at 48 months ( ≤ 0.02 in all, adjusted), and in the SEM model, they showed an anti-ageing impact. Supplementation with selenium/Q10 influenced the analysed biomarkers in ways indicating an anti-ageing effect, and by applying SEM methodology, the interrelationships between two independent structural factors and age were validated.
衰老是心血管疾病 (CVD) 的相关因素。由于没有单一的生物标志物能反映整个衰老过程,我们旨在研究五个与 CVD 和年龄相关的标志物,以及硒和辅酶 Q10 干预的效果,以阐明可能影响衰老进程的机制。这是一项先前前瞻性双盲安慰剂对照随机临床试验的子研究,共纳入 441 名低硒受试者(平均年龄 77 岁,49%为女性)。活性治疗组(n=220)接受 200μg/天硒和 200mg/天辅酶 Q10 联合治疗。在纳入时和 48 个月时采集血液样本,通过 ELISA 法测量细胞间黏附分子 (ICAM-1)、脂联素、瘦素、干细胞因子 (SCF) 和护骨素 (OPG)。采用重复测量方差和协方差分析比较两组。为了更好地理解和简化生物标志物与年龄之间的关系的复杂性,进行了因子分析和结构方程模型 (SEM),并呈现了一个结构模型。对纳入时的生物标志物值与年龄的相关性以及与炎症、内皮功能障碍和纤维化相关的相关标志物进行相关性分析,表明这些生物标志物与这些病理过程相关;然而,只有 ICAM1 和脂联素与年龄直接相关。SEM 分析表明,生物标志物 ICAM-1、脂联素、SCF 和 OPG,但不是瘦素,均与年龄有显著相关性,形成两个独立的结构因子,均与年龄显著相关。虽然在纳入时没有观察到差异,但在 48 个月时(所有调整后均为 ≤0.02),活性治疗组和安慰剂组的生物标志物发生了不同的变化(分别为降低和升高水平),并且在 SEM 模型中,它们显示出抗衰老作用。硒/辅酶 Q10 补充剂对分析生物标志物的影响表明具有抗衰老作用,并且通过应用 SEM 方法学,验证了两个独立结构因子与年龄之间的相互关系。