Age- and Sex-Dependent Changes of Free Circulating Blood Metabolite and Lipid Abundances, Correlations, and Ratios

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, alpha-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.

Automated summary

This study investigated the variations in concentrations, correlations, and ratios of 202 free circulating blood metabolites and lipids with age. The results showed that certain metabolites and lipids were associated with age in a sex-dependent manner, with linoleic acid, alpha-linoleic acid, and carnitine being associated with age in women, and monoacylglycerols and lysophosphatidylcholines being associated with age in men. Furthermore, correlations among phosphatidylcholines tended to have a positive trend with age in women, while correlations among monoacylglycerols and lysophosphatidylcholines tended to have a negative trend with age in men. The ratios between molecular features also showed age-dependent changes, with the decanoyl-l-carnitine/lysophosphatidylcholine ratio decreasing with age in women, and the l-carnitine/phosphatidylcholine and l-acetylcarnitine/phosphatidylcholine ratios increasing with age in men.