Demographic and clinical variables affecting mid-to late-life trajectories of plasma ceramide and dihydroceramide species
Demographic and clinical variables affecting mid-to late-life trajectories of plasma ceramide and dihydroceramide species
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DOI：
10.1111/acel.12369
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发表时间：
2015-12-01
期刊：
影响因子：
7.8
通讯作者：
Haughey, Norman J.
中科院分区：
文献类型：
--
作者：
Mielke, Michelle M.;Bandaru, Veera Venkata Ratnam;Haughey, Norman J.
在基础科学水平上，人们越来越认识到神经酰胺代谢的紊乱与许多年龄相关疾病的发生和进展有关。然而，这项工作的翻译到诊所已经落后。了解在人群水平上与血浆神经酰胺和二氢神经酰胺（DHCer）纵向相关的因素以及这些脂质水平如何随年龄和性别变化，对于未来专注于神经酰胺代谢的治疗和生物标志物的临床开发非常重要。因此，我们研究了巴尔的摩老龄化纵向研究参与者（n = 992; 3960个样本）中与血浆神经酰胺和DHCer浓度相关的横截面和纵向因素，这些参与者年龄在55岁及以上，平均4.1次访视（范围2-6）。在高效液相色谱-电喷雾串联质谱仪上进行定量分析。使用线性混合模型评估血浆神经酰胺和DHCer种类与人口统计学、疾病、药物和生活方式因素之间的关系。与男性相比，女性的大多数神经酰胺和DHCer物质的血浆浓度更高，并且显示出与年龄相关的增加的更陡峭的轨迹。神经酰胺和DHCer与腰臀比的相关性大于与体重指数的相关性。血浆胆固醇和甘油三酯、糖尿病前期和糖尿病与神经酰胺和DHCer相关，但这种关系对酰基链长度和饱和度具有特异性。这些结果证明了检查神经酰胺和DHCer的个体物种以及确定个体内年龄和性别特异性变化是否与疾病发作和进展同步发生的重要性。
It has been increasingly recognized at the basic science level that perturbations in ceramide metabolism are associated with the development and progression of many age-related diseases. However, the translation of this work to the clinic has lagged behind. Understanding the factors longitudinally associated with plasma ceramides and dihydroceramides (DHCer) at the population level and how these lipid levels change with age, and by sex, is important for the clinical development of future therapeutics and biomarkers focused on ceramide metabolism. We, therefore, examined factors cross-sectionally and longitudinally associated with plasma concentrations of ceramides and DHCer among Baltimore Longitudinal Study of Aging participants (n = 992; 3960 total samples), aged 55 years and older, with plasma at a mean of 4.1 visits (range 2-6). Quantitative analyses were performed on a high-performance liquid chromatography-coupled electrospray ionization tandem mass spectrometer. Linear mixed models were used to assess the relationships between plasma ceramide and DHCer species and demographics, diseases, medications, and lifestyle factors. Women had higher plasma concentrations of most ceramide and DHCer species and showed steeper trajectories of age-related increases compared to men. Ceramides and DHCer were more associated with waist-hip ratio than body mass index. Plasma cholesterol and triglycerides, prediabetes, and diabetes were associated with ceramides and DHCer, but the relationship showed specificity to the acyl chain length and saturation. These results demonstrate the importance of examining the individual species of ceramides and DHCer, and of establishing whether intra-individual age- and sex-specific changes occur in synchrony to disease onset and progression.