PLOS ONE: Metabolic Signatures of Extreme Longevity in Northern Italian Centenarians Reveal a Complex Remodeling of Lipids, Amino Acids, and Gut Microbiota Metabolism
Metabolic Signatures of Extreme Longevity in Northern Italian Centenarians Reveal a Complex Remodeling of Lipids, Amino Acids, and Gut Microbiota Metabolism
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Formal Correction: This article has been formally corrected to address the following errors.
- A funding organization and two grants from that organization given to Claudio Franceschi were incorrectly omitted from the Funding Statement.
The second sentence of the Funding Statement should read: "The research leading to these... (read formal correction)
Abstract
The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic 1H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female centenarians, elderly, and young individuals. With increasing age, targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians' unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristic of their extreme aging phenotype. Our data in centenarians support promotion of cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP) enzyme activity. Such effective mechanism might result in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG) and p-cresol sulfate (PCS) in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.Citation: Collino S, Montoliu I, Martin F-PJ, Scherer M, Mari D, et al. (2013) Metabolic Signatures of Extreme Longevity in Northern Italian Centenarians Reveal a Complex Remodeling of Lipids, Amino Acids, and Gut Microbiota Metabolism. PLoS ONE 8(3): e56564. doi:10.1371/journal.pone.0056564
Editor: Anne Wertheimer, University of Arizona, United States of America
Received: August 16, 2012; Accepted: January 11, 2013; Published: March 6, 2013
Copyright: © 2013 Collino et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors are grateful to CEPS and ANNFAS no-profit associations and to Dr. Daniela Follo and Alessandro Ghezzo for the recruitment of DS persons. This research was funded by University of Florence to D. Monti and MIUR (PRIN2006) to D. Monti, CF, and D. Mari. The funding sources have not been involved in the design, analysis or interpretation of the results.
Competing interests: Authors SC, FPM, MS, SR are employees of Nestlè Institute of Health Science SA. Author IM is an employee of Nestec S.A. There are no products in development or marketed products to declare. Five patents were filed based on the results presented in the paper. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
Editor: Anne Wertheimer, University of Arizona, United States of America
Received: August 16, 2012; Accepted: January 11, 2013; Published: March 6, 2013
Copyright: © 2013 Collino et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors are grateful to CEPS and ANNFAS no-profit associations and to Dr. Daniela Follo and Alessandro Ghezzo for the recruitment of DS persons. This research was funded by University of Florence to D. Monti and MIUR (PRIN2006) to D. Monti, CF, and D. Mari. The funding sources have not been involved in the design, analysis or interpretation of the results.
Competing interests: Authors SC, FPM, MS, SR are employees of Nestlè Institute of Health Science SA. Author IM is an employee of Nestec S.A. There are no products in development or marketed products to declare. Five patents were filed based on the results presented in the paper. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
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