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=1882 subjects ranging 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 cohort, linoleic acid, α-linoleic acid, and carnitine, and, in men sub-group, 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 the ratio between decanoyl L-carnitine and lysophosphatidylcholine in women have a negative association with age, while the ratios between L-carnitine, L-acetylcarnitine, and phosphatidylcholines in men have a positive association 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 to aging focused on the changes of concentrations and relationships thereof, as expressed by their correlations and ratios, it is possible to obtain relevant information about metabolic dynamics associated with age.