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The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The small molecule chemicals found in a given metabolome may include both endogenous metabolites that are naturally produced by an organism (such as amino acids, organic acids, nucleic acids, fatty acids, amines, sugars, vitamins, co-factors, pigments, antibiotics, etc.) as well as exogenous chemicals (such as drugs, environmental contaminants, food additives, toxins and other xenobiotics) that are not naturally produced by an organism. In other words, there is both an endogenous metabolome and an exogenous metabolome. The endogenous metabolome can be further subdivided to include a "primary" and a "secondary" metabolome (particularly when referring to plant or microbial metabolomes). A primary metabolite is directly involved in the normal growth, dev

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Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity

Fiona Beguelin, Sebastiano Collino, Martin Kussmann

As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot-gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

Impact Journals Llc2014

Performance and reproducibility of C-13 and N-15 hyperpolarization using a cryogen-free DNP polarizer

Arianna Ferrari, Hikari Ananda Infinity Yoshihara

The setup, operational procedures and performance of a cryogen-free device for producing hyperpolarized contrast agents using dissolution dynamic nuclear polarization (dDNP) in a preclinical imaging center is described. The polarization was optimized using the solid-state, DNP-enhanced NMR signal to calibrate the sample position, microwave and NMR frequency and power and flip angle. The polarization of a standard formulation to yield similar to 4 mL, 60 mM 1-C-13-pyruvic acid in an aqueous solution was quantified in five experiments to P(C-13) = (38 +/- 6) % (19 +/- 1) s after dissolution. The mono-exponential time constant of the build-up of the solid-state polarization was quantified to (1032 +/- 22) s. We achieved a duty cycle of 1.5 h that includes sample loading, monitoring the polarization build-up, dissolution and preparation for the next run. After injection of the contrast agent in vivo, pyruvate, pyruvate hydrate, lactate, and alanine were observed, by measuring metabolite maps. Based on this work sequence, hyperpolarized N-15 urea was obtained (P(N-15) = (5.6 +/- 0.8) % (30 +/- 3) s after dissolution).

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Joint mouse-human phenome-wide association to test gene function and disease risk

Johan Auwerx, Virginija Jovaisaite, Zhi Li, Xu Wang, Evan Graehl Williams

Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for similar to 5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of similar to 4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets-by far the largest coherent phenome for any experimental cohort (www.genenetwork.org). We tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.

Nature Publishing Group2016

Metabolomics

Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "sy

Metabolite

In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling,

Omics

The branches of science known informally as omics are various disciplines in biology whose names end in the suffix -omics, such as genomics, proteomics, metabolomics, metagenomics, phenomics and tra

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