Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains

• Main Authors: Sunil Kochhar, Tomas A. Prolla, Richard Weindruch, Laeticia Da Silva, Ivan Montoliu, Jamie L. Barger, François-Pierre J. Martin, Sebastiano Collino
• Format: Article
• Language: English
• Published: MDPI AG 2013-10-01
• Series: Metabolites
• Subjects: metabolomics; healthy ageing; calorie restriction; lipidomics
• Online Access: http://www.mdpi.com/2218-1989/3/4/881

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.