The Effects of Graded Levels of Calorie Restriction: XIII. Global Metabolomics Screen Reveals Graded Changes in Circulating Amino Acids, Vitamins, and Bile Acids in the Plasma of C57BL/6 Mice

Cara L Green, Quinlyn A Soltow, Sharon E Mitchell, Davina Derous, Yingchun Wang, Luonan Chen, Jing-Dong J Han, Daniel E. L. Promislow, David Lusseau, Alexander Douglas, Dean P Jones, John R. Speakman* (Corresponding Author)

*Corresponding author for this work

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19 Citations (Scopus)
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Abstract

Calorie restriction (CR) remains the most robust intervention to extend life span and improve health span. Using a global mass spectrometry–based metabolomics approach, we identified metabolites that were significantly differentially expressed in the plasma of C57BL/6 mice, fed graded levels of calorie restriction (10% CR, 20% CR, 30% CR, and 40% CR) compared with mice fed ad libitum for 12 hours a day. The differential expression of metabolites increased with the severity of CR. Pathway analysis revealed that graded CR had an impact on vitamin E and vitamin B levels, branched chain amino acids, aromatic amino acids, and fatty acid pathways. The majority of amino acids correlated positively with fat-free mass and visceral fat mass, indicating a strong relationship with body composition and vitamin E metabolites correlated with stomach and colon size, which may allude to the beneficial effects of investing in gastrointestinal organs with CR. In addition, metabolites that showed a graded effect, such as the sphinganines, carnitines, and bile acids, match our previous study on liver, which suggests not only that CR remodels the metabolome in a way that promotes energy efficiency, but also that some changes are conserved across tissues.
Original languageEnglish
Pages (from-to)16-26
Number of pages11
JournalThe Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Volume74
Issue number1
Early online date30 Apr 2018
DOIs
Publication statusPublished - 1 Jan 2019

Bibliographical note

Work toward having all the data from this series of papers online is currently ongoing. All significant metabolites in relation to CR manipulation are listed in Supplementary Material S1. Data on the nonsignificant metabolites are freely available for anyone who requests it from the corresponding author at j.speakman@abdn.ac.uk

The study was supported by the UK Biotechnology and Biological Sciences Research Council BBSRC (BB/G009953/1 and BB/J020028/1 to J.R.S.) and a studentship of C.L.G. from the BBSRC EastBio Doctoral Training Partnership. C.L.G. received support from the laboratory of D.P.; D.P. was supported in part by NIH grant AGO49494.

Data Availability Statement

Work toward having all the data from this series of papers online is currently
ongoing. All significant metabolites in relation to CR manipulation are listed
in Supplementary Material S1. Data on the nonsignificant metabolites are
freely available for anyone who requests it from the corresponding author at j.speakman@abdn.ac.uk.

Keywords

  • metabolomics
  • calorie restriction
  • aging
  • vitamin E
  • amino acids
  • bile acids
  • Metabolomics
  • Bile acids
  • Vitamin E
  • Calorie restriction
  • Aging
  • Amino acids

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