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Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains
Nestlé Institute of Health Sciences SA, Molecular Biomarkers Core, Campus EPFL, Quartier de l'innovation, bâtiment H, Lausanne 1015, Switzerland
Nestlé Research Center, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland
LifeGen Technologies, LLC (Limited Liability Company), Madison, WI 53719, USA
Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53704, USA
Department of Medicine, University of Wisconsin and William S. Middleton Veteran's Hospital, Madison, WI 53705, USA
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 28 June 2013; in revised form: 23 September 2013 / Accepted: 25 September 2013 / Published: 11 October 2013
Abstract: Calorie restriction (CR) has long been used to study lifespan effects and oppose the development of a broad array of age-related biological and pathological changes (increase healthspan). Yet, a comprehensive comparison of the metabolic phenotype across different genetic backgrounds to identify common metabolic markers affected by CR is still lacking. Using a system biology approach comprising metabonomics and liver transcriptomics we revealed the effect of CR across multiple mouse strains (129S1/SvlmJ, C57BL6/J, C3H/HeJ, CBA/J, DBA/2J, JC3F1/J). Oligonucleotide microarrays identified 76 genes as differentially expressed in all six strains confirmed. These genes were subjected to quantitative RT-PCR analysis in the C57BL/6J mouse strain, and a CR-induced change expression was confirmed for 14 genes. To fully depict the metabolic pathways affected by CR and complement the changes observed through differential gene expression, the metabolome of C57BL6/J was further characterized in liver tissues, urine and plasma levels using a combination or targeted mass spectrometry and proton nuclear magnetic resonance spectroscopy. Overall, our integrated approach commonly confirms that energy metabolism, stress response, lipids regulators and the insulin/IGF-1 are key determinants factors involved in CR regulation.
Keywords: metabolomics; healthy ageing; calorie restriction; lipidomics
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Collino, S.; Martin, F.-P.J.; Montoliu, I.; Barger, J.L.; Da Silva, L.; Prolla, T.A.; Weindruch, R.; Kochhar, S. Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains. Metabolites 2013, 3, 881-911.
Collino S, Martin F-PJ, Montoliu I, Barger JL, Da Silva L, Prolla TA, Weindruch R, Kochhar S. Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains. Metabolites. 2013; 3(4):881-911.
Collino, Sebastiano; Martin, François-Pierre J.; Montoliu, Ivan; Barger, Jamie L.; Da Silva, Laeticia; Prolla, Tomas A.; Weindruch, Richard; Kochhar, Sunil. 2013. "Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains." Metabolites 3, no. 4: 881-911.