Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309 U.S.A.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A.
Clin Sci (Lond). 2018 Aug 30;132(16):1765-1777. doi: 10.1042/CS20180409. Print 2018 Aug 31.
Advancing age is associated with impairments in numerous physiological systems, leading to an increased risk of chronic disease and disability, and reduced healthspan (the period of high functioning healthy life). The plasma metabolome is thought to reflect changes in the activity of physiological systems that influence healthspan. Accordingly, we utilized an LC-MS metabolomics analysis of plasma collected from healthy young and older individuals to characterize global changes in small molecule abundances with age. Using a weighted gene correlation network analysis (WGCNA), similarly expressed metabolites were grouped into modules that were related to indicators of healthspan, including clinically relevant markers of morphology (body mass index, body fat, and lean mass), cardiovascular health (systolic/diastolic blood pressure, endothelial function), renal function (glomerular filtration rate), and maximal aerobic exercise capacity in addition to conventional clinical blood markers (e.g. fasting glucose and lipids). Investigation of metabolic classes represented within each module revealed that amino acid and lipid metabolism as significantly associated with age and indicators of healthspan. Further LC-MS/MS targeted analyses of the same samples were used to identify specific metabolites related to age and indicators of healthspan, including methionine and nitric oxide pathways, fatty acids, and ceramides. Overall, these results demonstrate that plasma metabolomics profiles in general, and amino acid and lipid metabolism in particular, are associated with ageing and indicators of healthspan in healthy adults.
随着年龄的增长，许多生理系统都会出现功能障碍，导致慢性病和残疾的风险增加，健康寿命（即高功能健康生活的时期）缩短。人们认为，血浆代谢组学可以反映影响健康寿命的生理系统活性变化。因此，我们利用 LC-MS 代谢组学分析方法，对来自健康年轻个体和老年个体的血浆进行分析，以描述小分子随年龄变化的全局特征。我们使用加权基因相关网络分析（WGCNA），将具有相似表达模式的代谢物分组为与健康寿命指标相关的模块，这些指标包括形态学（体重指数、体脂肪和瘦体重）、心血管健康（收缩压/舒张压、内皮功能）、肾功能（肾小球滤过率）和最大有氧运动能力的临床相关标志物，以及常规临床血液标志物（如空腹血糖和血脂）。对每个模块中包含的代谢物类别的研究表明，氨基酸和脂质代谢与年龄和健康寿命指标显著相关。我们还对同一批样本进行了相同的 LC-MS/MS 靶向分析，以确定与年龄和健康寿命指标相关的特定代谢物，包括蛋氨酸和一氧化氮途径、脂肪酸和神经酰胺。总的来说，这些结果表明，血浆代谢组学图谱一般，特别是氨基酸和脂质代谢与健康成年人的衰老和健康寿命指标有关。
