Regarding all three datasets, no direct overlap between biomarkers in the shortest path subnetworks, however from each dataset one marker remains in a merged network (L-ornithine, L-Citrulline, and L-aspartic Acid, respectively). The underlying reactions are connected to pathways involving 'amino acid synthesis, metabolism and catabolism', 'glucose metabolism', 'branched-chain amino acid metabolism', 'pyrimidine metabolism', several vitamin pathways, and urea (cycle) pathways; these pathways are needed for homeostasis and serve a key role in (healthy) aging. Overview of directed shortest path calculations for the second dataset (MTBLS404) related to aging biomarkers in urine (30 relevant metabolites) according to log2 ratios, where relevant metabolites have a diamond shape; round nodes depict metabolites needed for connectivity and hexagons proteins. The thickness of the arrows between the nodes indicates the count of the reactions' occurrence in different pathways. The right top corner shows a cluster of several higher abundance (xenobiotic) compounds; the left bottom the connections between Tryptamine, L-tryptophan, and 5-hydroxy indole-3-acetic acid (red dashed), as well as the three-step path from L-tryptophan to kynurenic acid (blue dotted). The top middle shows a connection between L-aspartic acid (low abundance) and fumaric acid (higher abundance) two steps removed. Low abundant 1 or 2 steps including log2 values: tryptamine (-1.8), L-tryptophan (-0.91), and 5-hydroxy indole-3-acetic acid (-1.1); N-Acetyl-L-aspartic acid (-0.75) and Laspartic acid (-0.84); Low abundant 3 steps: L-tryptophan (-0.91) and kynurenic acid (-0.63); Higher abundant: 1-methylxanthine (+1.9), 1-methyl uric acid (+1.6), caffeine (+5.2) and 1,7-dimethyl uric acid(+2.8). related to aging biomarkers in urine and blood (14 relevant metabolites) according to three machine learning methods, where blood markers have a diamond shape and urine markers a V-shape; round nodes depict metabolites needed for connectivity and hexagons proteins. The thickness of the arrows between the nodes indicates the count of the reactions' occurrence in different pathways. Various pathways were needed to build this visualization, including lipids (pink contiguous arrows), cerebral organic acidurias (blue dotted reactions), and urea (cycle) pathways in yellow/green (dash/dotted lines).