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Metabotyping of Long-Lived Mice using H-1 NMR Spectroscopy

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Title: Metabotyping of Long-Lived Mice using H-1 NMR Spectroscopy
Authors: Wijeyesekera, A
Selman, C
Barton, RH
Holmes, E
Nicholson, JK
Withers, DJ
Item Type: Journal Article
Abstract: Significant advances in understanding aging have been achieved through studying model organisms with extended healthy lifespans. Employing 1H NMR spectroscopy, we characterized the plasma metabolic phenotype (metabotype) of three long-lived murine models: 30% dietary restricted (DR), insulin receptor substrate 1 null (Irs1–/–), and Ames dwarf (Prop1df/df). A panel of metabolic differences were generated for each model relative to their controls, and subsequently, the three long-lived models were compared to one another. Concentrations of mobile very low density lipoproteins, trimethylamine, and choline were significantly decreased in the plasma of all three models. Metabolites including glucose, choline, glycerophosphocholine, and various lipids were significantly reduced, while acetoacetate, d-3-hydroxybutyrate and trimethylamine-N-oxide levels were increased in DR compared to ad libitum fed controls. Plasma lipids and glycerophosphocholine were also decreased in Irs1–/– mice compared to controls, as were methionine and citrate. In contrast, high density lipoproteins and glycerophosphocholine were increased in Ames dwarf mice, as were methionine and citrate. Pairwise comparisons indicated that differences existed between the metabotypes of the different long-lived mice models. Irs1–/– mice, for example, had elevated glucose, acetate, acetone, and creatine but lower methionine relative to DR mice and Ames dwarfs. Our study identified several potential candidate biomarkers directionally altered across all three models that may be predictive of longevity but also identified differences in the metabolic signatures. This comparative approach suggests that the metabolic networks underlying lifespan extension may not be exactly the same for each model of longevity and is consistent with multifactorial control of the aging process.
Issue Date: 1-Apr-2012
Date of Acceptance: 6-Jan-2012
URI: http://hdl.handle.net/10044/1/52171
DOI: https://dx.doi.org/10.1021/pr2010154
ISSN: 1535-3893
Publisher: American Chemical Society
Start Page: 2224
End Page: 2235
Journal / Book Title: Journal of Proteome Research
Volume: 11
Issue: 4
Copyright Statement: This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Sponsor/Funder: Medical Research Council (MRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Wellcome Trust
Funder's Grant Number: G0801056B
BB/H020527/2
098565/Z/12/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemical Research Methods
Biochemistry & Molecular Biology
BIOCHEMICAL RESEARCH METHODS
metabolic phenotyping
metabotype
nuclear magnetic resonance
lifespan
aging
dietary restriction
Irs1
Ames dwarf
AMES DWARF MICE
EXTENDS LIFE-SPAN
TERM CALORIC RESTRICTION
GENETICALLY HETEROGENEOUS MICE
NUCLEAR-MAGNETIC-RESONANCE
METHIONINE RESTRICTION
CARDIOVASCULAR-DISEASE
CAENORHABDITIS-ELEGANS
TARGETED DISRUPTION
EXPRESSION PATTERNS
Animals
Blood Glucose
Choline
Glycerylphosphorylcholine
Homeodomain Proteins
Insulin Receptor Substrate Proteins
Least-Squares Analysis
Lipids
Longevity
Magnetic Resonance Spectroscopy
Male
Metabolome
Metabolomics
Methionine
Mice
Mice, Inbred C57BL
Multivariate Analysis
Phenotype
06 Biological Sciences
03 Chemical Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Clinical Sciences
Molecular Sciences
Faculty of Medicine



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