Research Papers: Gerotarget (Focus on Aging):

The effects of graded levels of calorie restriction: I. impact of short term calorie and protein restriction on body composition in the C57BL/6 mouse

Sharon E. Mitchell, Zhanhui Tang, Celine Kerbois, Camille Delville, Penelope Konstantopedos, Aurélie Bruel, Davina Derous, Cara Green, Richard M. Aspden, Simon R. Goodyear, Luonan Chen, Jackie J.D. Han, Yingchun Wang, Daniel E.L. Promislow, David Lusseau, Alex Douglas and John R. Speakman _

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Oncotarget. 2015; 6:15902-15930. https://doi.org/10.18632/oncotarget.4142

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Sharon E. Mitchell1, Zhanhui Tang1, Celine Kerbois1, Camille Delville1, Penelope Konstantopedos1, Aurélie Bruel1, Davina Derous1, Cara Green1, Richard M. Aspden2, Simon R. Goodyear2, Luonan Chen3, Jackie J.D. Han4, Yingchun Wang5, Daniel E.L. Promislow6, David Lusseau1, Alex Douglas1 and John R. Speakman1,5

1 Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK

2 Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK

3 Key laboratory of Systems Biology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, China

4 Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences, Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

5 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, China

6 Department of Pathology and Department of Biology, University of Washington, Seattle, WA, USA

Correspondence to:

John R. Speakman, email:

Keywords: food intake, dietary restriction, protein restriction, calorie restriction, body composition

Received: March 23, 2015 Accepted: March 31, 2015 Published: June 06, 2015


Faced with reduced levels of food, animals must adjust to the consequences of the shortfall in energy. We explored how C57BL/6 mice withdrew energy from different body tissues during three months of food restriction at graded levels up to 40% (calorie restriction: CR). We compared this to the response to equivalent levels of protein restriction (PR) without a shortfall in calories. Under CR there was a dynamic change in body mass over 30 days and thereafter it stabilized. The time to reach stability was independent of the level of restriction. At the end of three months whole body dissections revealed differential utilization of the different tissues. Adipose tissue depots were the most significantly utilized tissue, and provided 55.8 to 60.9% of the total released energy. In comparison, reductions in the sizes of structural tissues contributed between 29.8 and 38.7% of the energy. The balance was made up by relatively small changes in the vital organs. The components of the alimentary tract grew slightly under restriction, particularly the stomach, and this was associated with a parallel increase in assimilation efficiency of the food (averaging 1.73%). None of the changes under CR were recapitulated by equivalent levels of PR.

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