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Author Notes:

Address correspondence to: John R. Speakman, PhD, Institute of Biological and Environmental Sciences, Zoology Building, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, UK. E-mail: j.speakman@abdn.ac.uk

J.R.S. conceptualized and designed the experiment, raised the funding to execute it, and was the HO project license holder. Animal work was carried out by S.E.M.

Q.S. and D.J. performed the DC-FTMS.

C.G., D.P., A.D., and D.L. performed the statistical analysis.

C.G., D.P., A.D., D.L., S.E.M., and J.R.S. interpreted the results.

C.G. wrote the manuscript, and A.D., D.P., D.L., S.E.M., and J.R.S. revised it.

All authors contributed to the analysis during discussions at joint meetings funded by BBSRC grant.

Conflict of Interest: None reported.


Research Funding:

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.


  • Metabolomics
  • Calorie restriction
  • Aging
  • Vitamin E
  • Amino acids
  • Bile acids

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

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Journal Title:

Journals of Gerontology, Series A


Volume 74, Number 1


, Pages 16-26

Type of Work:

Article | Final Publisher PDF


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.

Copyright information:

© 2018 The Author(s). Published by Oxford University Press on behalf of The Gerontological Society of America.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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