title: Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains.
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.
authors: Nestlé Institute of Health Sciences SA, Molecular Biomarkers Core, Campus EPFL, Quartier de l'innovation, bâtiment H, Lausanne 1015, Switzerland. Laeticia.DaSilva@rd.nestle.com.
authors: Sebastiano
authors: S
authors: Collino
authors: Nestlé Institute of Health Sciences SA, Molecular Biomarkers Core, Campus EPFL, Quartier de l'innovation, bâtiment H, Lausanne 1015, Switzerland. Laeticia.DaSilva@rd.nestle.com.
authors: François-Pierre J
authors: FP
authors: Martin
authors: Nestlé Research Center, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland.
authors: Ivan
authors: I
authors: Montoliu
authors: LifeGen Technologies, LLC (Limited Liability Company), Madison, WI 53719, USA. jamie.l.barger@gmail.com.
authors: Jamie L
authors: JL
authors: Barger
authors: Nestlé Institute of Health Sciences SA, Molecular Biomarkers Core, Campus EPFL, Quartier de l'innovation, bâtiment H, Lausanne 1015, Switzerland. Laeticia.DaSilva@rd.nestle.com.
authors: Laeticia
authors: L
authors: Da Silva
authors: Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53704, USA.
authors: Tomas A
authors: TA
authors: Prolla
authors: Department of Medicine, University of Wisconsin and William S. Middleton Veteran's Hospital, Madison, WI 53705, USA. rhweindr@wisc.edu.
authors: Richard
authors: R
authors: Weindruch
authors: Nestlé Research Center, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland. sunil.kochhar@rd.nestle.com.
authors: Sunil
authors: S
authors: Kochhar