Extended Data Fig. 2: Metabolomic profile of plasma.

a, PCA of standardized levels of metabolites in plasma. Each dot represents a donor. b, Dendrogram produced by unsupervised hierarchical clustering of metabolic data. Clustering using average algorithm and Euclidian distance as the distance metric. c, List of significantly different metabolites. d, Selected differentially regulated metabolites from sex steroids synthesis pathway in young (n = 20) and old (n = 20) cohorts. Statistical analyses by two-sided Mann-Whitney U test with Benjamini–Hochberg correction for multiple testing. e, Schema of sex steroids synthesis. f, Pathway analysis of metabolic data. Each boxplot summarizes log2FC of all members of the corresponding pathway. Pathways with mean log2FC significantly different from zero are highlighted (two-sided Mann-Whitney U test and Benjamini-Hochberg correction for multiple testing). Dots represent outliers. N for each pathway is shown in brackets. g, PCA as in Extended Data 2a. Z-scores were calculated for all metabolites. For each sample, color of the dot represents averaged z-scores of all metabolites belonging to the pathway. In panels (D) and (F), the lower and upper hinges of all boxplots represent the 25th and 75th percentiles. Horizontal bars show median value. Whiskers extend to the values that are no further than 1.5*IQR from either upper or lower hinge. IQR stands for inter-quartile range, which is the difference between the 75th and 25th percentiles.