Document Detail

Metabotyping of long-lived mice using 1H NMR spectroscopy.
MedLine Citation:
PMID:  22225495     Owner:  NLM     Status:  MEDLINE    
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.
Anisha Wijeyesekera; Colin Selman; Richard H Barton; Elaine Holmes; Jeremy K Nicholson; Dominic J Withers
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Publication Detail:
Type:  Journal Article     Date:  2012-02-27
Journal Detail:
Title:  Journal of proteome research     Volume:  11     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-06     Completed Date:  2012-09-18     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2224-35     Citation Subset:  IM    
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MeSH Terms
Blood Glucose
Choline / blood
Glycerylphosphorylcholine / blood
Homeodomain Proteins / genetics
Insulin Receptor Substrate Proteins / genetics
Least-Squares Analysis
Lipids / blood
Longevity / physiology*
Magnetic Resonance Spectroscopy / methods*
Metabolomics / methods*
Methionine / blood
Mice, Inbred C57BL
Multivariate Analysis
Grant Support
MC_U120097114//Medical Research Council
Reg. No./Substance:
0/Blood Glucose; 0/Homeodomain Proteins; 0/Insulin Receptor Substrate Proteins; 0/Irs1 protein, mouse; 0/Lipids; 0/Prophet of Pit-1 protein; 60M22SGW66/Glycerylphosphorylcholine; AE28F7PNPL/Methionine; N91BDP6H0X/Choline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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