In this study, we investigated how the concentrations, pairwise correlations and ratios of 202 free circulating blood metabolites and lipids vary with age in a panel of n = 1 882 participants with an age range from 48 to 94 years. We report a statistically significant sex-dependent association with age of a panel of metabolites and lipids involving, in women, linoleic acid, α-linoleic acid, and carnitine, and, in men, monoacylglycerols and lysophosphatidylcholines. Evaluating the association of correlations among metabolites and/or lipids with age, we found that phosphatidylcholines correlations tend to have a positive trend associated with age in women, and monoacylglycerols and lysophosphatidylcholines correlations tend to have a negative trend associated with age in men. The association of ratio between molecular features with age reveals that decanoyl-l-carnitine/lysophosphatidylcholine ratio in women “decrease” with age, while l-carnitine/phosphatidylcholine and l-acetylcarnitine/phosphatidylcholine ratios in men “increase” with age. These results suggest an age-dependent remodeling of lipid metabolism that induces changes in cell membrane bilayer composition and cell cycle mechanisms. Furthermore, we conclude that lipidome is directly involved in this age-dependent differentiation. Our results demonstrate that, using a comprehensive approach focused on the changes of concentrations and relationships of blood metabolites and lipids, as expressed by their correlations and ratios, it is possible to obtain relevant information about metabolic dynamics associated with age.

中文翻译：

---

自由循环血液代谢物和脂质丰度、相关性和比率的年龄和性别依赖性变化

在这项研究中，我们调查了 202 种游离循环血液代谢物和脂质的浓度、成对相关性和比率如何随年龄变化而变化，一组 n = 1 882 名参与者的年龄范围为 48 至 94 岁。我们报告了一组代谢物和脂质与年龄的统计学显着的性别相关性，其中女性包括亚油酸、α-亚油酸和肉碱，而男性则包括单酰基甘油和溶血磷脂酰胆碱。评估代谢物和/或脂质之间的相关性与年龄的关联，我们发现磷脂酰胆碱的相关性往往与女性的年龄呈正相关，而单酰基甘油和溶血磷脂酰胆碱的相关性往往与男性的年龄呈负相关。分子特征与年龄之间的比例关系表明，女性的癸酰左旋肉碱/溶血磷脂酰胆碱的比例随着年龄的增长而“降低”，而男性的左旋肉碱/磷脂酰胆碱和左旋肉碱/磷脂酰胆碱的比例随着年龄的增长而“增加”。这些结果表明脂质代谢的年龄依赖性重塑会诱导细胞膜双层组成和细胞周期机制的变化。此外，我们得出结论，脂质组直接参与这种年龄依赖性分化。我们的研究结果表明，使用综合方法关注血液代谢物和脂质的浓度和关系的变化，如它们的相关性和比率所示，可以获得与年龄相关的代谢动力学的相关信息。