Metabolites present in human blood document individual physiological states influenced by genetic, epigenetic, and lifestyle factors. Using high-resolution liquid chromatography-mass spectrometry (LC-MS), we performed nontargeted, quantitative metabolomics analysis in blood of 15 young (29 ± 4 y of age) and 15 elderly (81 ± 7 y of age) individuals. Coefficients of variation (CV = SD/mean) were obtained for 126 blood metabolites of all 30 donors. Fiftyfive RBC-enriched metabolites, for which metabolomics studies have been scarce, are highlighted here. We found 14 blood compounds that show remarkable age-related increases or decreases; they include 1,5-anhydroglucitol, dimethyl-guanosine, acetyl-carnosine, carnosine, ophthalmic acid, UDP-acetyl-glucosamine, N-acetyl-arginine, N 6 -acetyl-lysine, pantothenate, citrulline, leucine, isoleucine, NAD + , and NADP + . Six of them are RBC-enriched, suggesting that RBC metabolomics is highly valuable for human aging research. Age differences are partly explained by a decrease in antioxidant production or increasing inefficiency of urea metabolism among the elderly. Pearson's coefficients demonstrated that some age-related compounds are correlated, suggesting that aging affects them concomitantly. Although our CV values are mostly consistent with those CVs previously published, we here report previously unidentified CVs of 51 blood compounds. Compounds having moderate to high CV values (0.4-2.5) are often modified. Compounds having low CV values, such as ATP and glutathione, may be related to various diseases because their concentrations are strictly controlled, and changes in them would compromise health. Thus, human blood is a rich source of information about individual metabolic differences. H uman blood metabolites have been well-investigated to determine their abundance and biological significance, and for their potential use as diagnostic markers. For medical diagnosis, noncellular metabolites from plasma or serum are mostly commonly used due to the simplicity in collecting and examining them. Although mature human red blood cells (RBCs) lack nuclei and cellular organelles (1), RBCs use glycolysis for ATP production, maintain redox homeostasis, and osmoregulate (2). Their active metabolism supports cellular homeostasis and ensures lifespans of ∼4 mo (3). Their metabolites may reflect health status or environmental stresses differently than do metabolites of plasma. Because RBCs occupy about half the total blood volume (∼5 L), their metabolite profiles, which have scarcely been investigated, seemed worthy of investigation.Metabolomics is a branch of chemical biology that profiles metabolites in cells and organisms, using techniques such as liquid chromatography (LC)-mass spectrometry (MS). It usually deals with molecules <1.5 kDa and is an important tool for studying metabolic regulation in combination with other comprehensive analyses, such as proteomics and transcriptomics. Recently, we reported that, among 133 compounds identified in human blood, 101 are also found...

Metabolomics, a modern branch of chemical biology, provides qualitative and quantitative information about the metabolic states of organisms or cells at the molecular level. Here we report non-targeted, metabolomic analyses of human blood, using liquid chromatography-mass spectrometry (LC-MS). We compared the blood metabolome to the previously reported metabolome of the fission yeast, Schizosaccharomyces pombe. The two metabolomic datasets were highly similar: 101 of 133 compounds identified in human blood (75%) were also present in S. pombe, and 45 of 57 compounds enriched in red blood cells (RBCs) (78%) were also present in yeast. The most abundant metabolites were ATP, glutathione, and glutamine. Apart from these three, the next most abundant metabolites were also involved in energy metabolism, anti-oxidation, and amino acid metabolism. We identified fourteen new blood compounds, eight of which were enriched in RBCs: citramalate, GDP-glucose, trimethyl-histidine, trimethyl-phenylalanine, trimethyl-tryptophan, trimethyl-tyrosine, UDP-acetyl-glucosamine, UDP-glucuronate, dimethyl-lysine, glutamate methyl ester, N-acetyl-(iso)leucine, N-acetyl-glutamate, N2-acetyl-lysine, and N6-acetyl-lysine. Ten of the newly identified blood metabolites were also detected in S. pombe, and ten of the 14 newly identified blood metabolites were methylated or acetylated amino acids. Trimethylated or acetylated free amino acids were also abundant in white blood cells. It may be possible to investigate their physiological roles using yeast genetics.

Mdm2, a ubiquitin ligase and downstream effector of p53, attenuates the proliferative potential of primary cells via ubiquitination and degradation of the glycolytic enzyme PGAM under senescence-inducing stress.

Potentiometric titration in various 1‐1 salt solutions was carried out to study the dissociation behavior of the poly(allylammonium) cation (PAAH+). The titration curves show that proton release from cationic PAAH+ is markedly suppressed by addition of simple salt and depends on the counterion species. From an analysis of the titration curves it is found that the electrostatic free energy change ΔGel upon the proton release is negative in all systems examined, and its absolute value decreases with increasing ionic strength of the medium. Also, at a constant added salt concentration (0.1 mol L−1) ΔGel depends significantly on the counterion species added and increases in the order $\[ {\rm ClO}_{\rm 4}^ - > {\rm NO}_3^ - > {\rm Cl}^ - > {\rm Br}^ - > {\rm SCN}^ - > {\rm I}^ - . \]$ The value of ΔGel correlates well with the electron donor constant En of the counterions. The dissociation behavior of PAAH+ is discussed in terms of electrostatic interaction among the ionized groups on the chain, the charge shielding effect, and the ion‐solvent interaction of the added counterions.

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