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Metabotyping of Long-Lived Mice using 1H NMR Spectroscopy.
MedLine Citation:
PMID:  22225495     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Significant advances in understanding aging have been achieved through studying model organisms with extended healthy lifespan. 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 increased in DR compared to ad libitum 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 differences existed between the metabotypes of the long-lived mice. 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 multi-factorial control of the aging process.
Authors:
Anisha Wijeyesekera; Colin Selman; Richard Hadlow Barton; Elaine Holmes; Dominic Withers; Jeremy Kirk Nicholson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-6
Journal Detail:
Title:  Journal of proteome research     Volume:  -     ISSN:  1535-3907     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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