Oncotarget

Research Papers: Gerotarget (Focus on Aging):

The effects of graded levels of calorie restriction: II. Impact of short term calorie and protein restriction on circulating hormone levels, glucose homeostasis and oxidative stress in male C57BL/6 mice

Sharon E. Mitchell _, Camille Delville, Penelope Konstantopedos, Jane Hurst, Davina Derous, Cara Green, 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; 6:23213-23237. https://doi.org/10.18632/oncotarget.4003

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Abstract

Sharon E. Mitchell1, Camille Delville1, Penelope Konstantopedos1, Jane Hurst2, Davina Derous1, Cara Green1, Luonan Chen3, Jackie J.D. Han4, Yingchun Wang5, Daniel E.L. Promislow6, David Lusseau1, Alex Douglas1, John R. Speakman1,5

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

2Mammalian Behaviour & Evolution Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK

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

4Key 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

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

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

Correspondence to:

John R. Speakman, e-mail: j.speakman@abdn.ac.uk

Keywords: calorie restriction, protein restriction, glucose homeostasis, oxidative stress, adipokines

Received: April 01, 2015     Accepted: May 20, 2015     Published: June 01, 2015

ABSTRACT

Limiting food intake attenuates many of the deleterious effects of aging, impacting upon healthspan and leading to an increased lifespan. Whether it is the overall restriction of calories (calorie restriction: CR) or the incidental reduction in macronutrients such as protein (protein restriction: PR) that mediate these effects is unclear. The impact of 3 month CR or PR, (10 to 40%), on C57BL/6 mice was compared to controls fed ad libitum. Reductions in circulating leptin, tumor necrosis factor-α and insulin-like growth factor-1 (IGF-1) were relative to the level of CR and individually associated with morphological changes but remained unchanged following PR. Glucose tolerance and insulin sensitivity were improved following CR but not affected by PR. There was no indication that CR had an effect on oxidative damage, however CR lowered antioxidant activity. No biomarkers of oxidative stress were altered by PR. CR significantly reduced levels of major urinary proteins suggesting lowered investment in reproduction. Results here support the idea that reduced adipokine levels, improved insulin/IGF-1 signaling and reduced reproductive investment play important roles in the beneficial effects of CR while, in the short-term, attenuation of oxidative damage is not applicable. None of the positive effects were replicated with PR.


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