Metabolomics analysis of human plasma metabolites reveals the age- and sex-specific associations

<b>Objectives:</b> The objective of this study was the investigation of age- and sex-associations in a set of blood plasma metabolites in healthy male and female subjects. <b>Methods:</b> A comparison study design with male and female subjects of various ages was used. Metabolic profiling was performed using electrospray ionization tandem mass spectrometry that yielded 186 metabolite concentrations for each study participant. The key age-related metabolites were identified using an integrative analysis of absolute concentrations, metabolite ratios and the differential correlation of pairwise metabolite concentrations. All of the age-associated metabolites were adjusted prior to the analysis to account for differences in Body Mass Index (BMI). <b>Results:</b> A total of 236 plasma samples from 140 female and 96 male subjects aged 20 to 82 years-old were collected and analyzed in the study. 13 and 14 age-associated metabolites (|r| &gt; 0.33 and <i>p</i> &lt; 6.6×10⁻⁵), 438 and 337 age-associated metabolite ratios (|r| &gt; 0.37 and <i>p</i> &lt; 3.5×10⁻⁶), and 5 and 10 core metabolites were discovered in the female and male groups, respectively. 80% of the metabolites displaying associations with age belonged to sphingolipids and phosphatidylcholines, and the two sexes shared less than 50% of the age-associated metabolites. <b>Conclusion:</b> The study found that changes in metabolite concentrations, metabolite ratios and differential correlations were age and sex-specific.

<b>研究目标:</b> 本研究旨在探究健康男性与女性受试者体内一组血浆代谢物与年龄、性别的关联关系。
<b>研究方法:</b> 本研究采用针对不同年龄层男性与女性受试者的对照研究设计。通过电喷雾串联质谱（electrospray ionization tandem mass spectrometry）开展代谢谱分析（metabolic profiling），获取每位研究受试者的186种代谢物浓度数据。本研究通过整合绝对浓度、代谢物比值（metabolite ratios）以及成对代谢物浓度的差异相关性（differential correlation）分析，鉴定出关键年龄相关代谢物（age-associated metabolites）。所有与年龄相关的代谢物在分析前均已针对体质量指数（Body Mass Index, BMI）的差异进行校正。
<b>研究结果:</b> 本研究共收集并分析了140名女性、96名男性受试者的236份血浆样本，受试者年龄介于20至82岁之间。在女性与男性组别中，分别鉴定出13种、14种年龄相关代谢物（|r|＞0.33且p＜6.6×10⁻⁵），438种、337种年龄相关代谢物比值（|r|＞0.37且p＜3.5×10⁻⁶），以及5种、10种核心代谢物（core metabolites）。其中80%与年龄存在关联的代谢物属于鞘磷脂（sphingolipids）与磷脂酰胆碱（phosphatidylcholines），且两性间共享的年龄相关代谢物占比不足50%。
<b>研究结论:</b> 本研究发现，代谢物浓度、代谢物比值以及差异相关性的变化均具有年龄与性别特异性。