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Chronic caloric restriction partially protects against age-related alteration in serum metabolome

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Abstract

Calorie restriction (CR) remains the most robust metabolic intervention to extend lifespan and improve healthspan in several species. Using global and targeted mass spectrometry-based metabolomics approaches, here we show that chronic CR prevents age-related changes in specific metabolic signatures. Global metabolomic analysis using ultra-performance liquid chromatography–tandem mass spectrometry detected more than 7,000 metabolites in sera from ad-libitum-fed young, aged, and aged C57BL/6 mice maintained on 40 % CR. Multivariate statistical analysis of mass spectrometry data revealed a clear separation among the young, aged, and aged–CR mice demonstrating the potential of this approach for producing reliable metabolic profiles that discriminate based on age and diet. We have identified 168 discriminating features with high statistical significance (p ≤ 0.001) and validated and quantified three of these metabolites using targeted metabolite analysis. Calorie restriction prevented the age-related alteration in specific metabolites, namely lysophosphatidylcholines (16:1 and 18:4), sphingomyelin (d18:1/12:0), tetracosahexaenoic acid, and 7α-dihydroxy-4-cholesten-3-one, in the serum. Pathway analysis revealed that CR impacted the age-related changes in metabolic byproducts of lipid metabolism, fatty acid metabolism, and bile acid biosynthesis. Our data suggest that metabolomics approach has the potential to elucidate the metabolic mechanism of CR’s potential anti-aging effects in larger-scale investigations.

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Acknowledgements

This work was supported by the funding from the Pennington Biomedical Research Foundation. VDD was supported in part by the NIH grants (R01AG31797, R01DK090556) and the Coypu Foundation.

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Authors and Affiliations

  1. Protein Structural Biology and Proteomics and Metabolomics Core, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA

    Jennifer M. De Guzman, Ginger Ku, Ryan Fahey & Indu Kheterpal

  2. Immunobiology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    Yun-Hee Youm & Vishwa Deep Dixit

  3. Nutritional Neuroscience and Aging, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    Donald K. Ingram

  4. Waters Corporation, Beverly, MA, USA

    Ignatius Kass

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  1. Jennifer M. De Guzman
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  2. Ginger Ku
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  4. Yun-Hee Youm
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Correspondence to Indu Kheterpal.

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De Guzman, J.M., Ku, G., Fahey, R. et al. Chronic caloric restriction partially protects against age-related alteration in serum metabolome. AGE 35, 1091–1104 (2013). https://doi.org/10.1007/s11357-012-9430-x

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