Priority Research Paper Volume 11, Issue 14 pp 4783—4800
The metabolomic signature of extreme longevity: naked mole rats versus mice
- 1 Fondation pour la Recherche en Physiologie, Brussels, Belgium
- 2 Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France
- 3 Equipe Labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France
- 4 Faculté de Médecine, Université de Paris Saclay, Kremlin Bicêtre, France
- 5 INSERM UMR_S1151 CNRS UMR8253 Institut Necker-Enfants Malades (INEM), Paris, France
- 6 Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria
- 7 BioTechMed Graz, Graz, Austria
- 8 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France
- 9 Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou, China
- 10 Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
- 11 Service de Physiologie et Explorations Fonctionnelles, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France
- 12 Université de Paris - Paris Descartes, Faculté de Médecine, Paris, France
Received: July 2, 2019 Accepted: July 16, 2019 Published: July 24, 2019
https://doi.org/10.18632/aging.102116How to Cite
Copyright © 2019 Viltard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The naked mole-rat (Heterocephalus glaber) is characterized by a more than tenfold higher life expectancy compared to another rodent species of the same size, namely, the laboratory mouse (Mus musculus). We used mass spectrometric metabolomics to analyze circulating plasma metabolites in both species at different ages. Interspecies differences were much more pronounced than age-associated alterations in the metabolome. Such interspecies divergences affected multiple metabolic pathways involving amino, bile and fatty acids as well as monosaccharides and nucleotides. The most intriguing metabolites were those that had previously been linked to pro-health and antiaging effects in mice and that were significantly increased in the long-lived rodent compared to its short-lived counterpart. This pattern applies to α-tocopherol (also known as vitamin E) and polyamines (in particular cadaverine, N8-acetylspermidine and N1,N8-diacetylspermidine), all of which were more abundant in naked mole-rats than in mice. Moreover, the age-associated decline in spermidine and N1-acetylspermidine levels observed in mice did not occur, or is even reversed (in the case of N1-acetylspermidine) in naked mole-rats. In short, the present metabolomics analysis provides a series of testable hypotheses to explain the exceptional longevity of naked mole-rats.