title: Organization of the Mammalian Metabolome according to Organ Function, Lineage Specialization, and Longevity.
abstract: Biological diversity among mammals is remarkable. Mammalian body weights range seven orders of magnitude and lifespans differ more than 100-fold among species. While genetic, dietary, and pharmacological interventions can be used to modulate these traits in model organisms, it is unknown how they are determined by natural selection. By profiling metabolites in brain, heart, kidney, and liver tissues of 26 mammalian species representing ten taxonomical orders, we report metabolite patterns characteristic of organs, lineages, and species longevity. Our data suggest different rates of metabolite divergence across organs and reveal patterns representing organ-specific functions and lineage-specific physiologies. We identified metabolites that correlated with species lifespan, some of which were previously implicated in longevity control. We also compared the results with metabolite changes in five long-lived mouse models and observed some similar patterns. Overall, this study describes adjustments of the mammalian metabolome according to lifespan, phylogeny, and organ and lineage specialization.
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Siming
authors.initials: S
authors.lastname: Ma
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute, Cambridge, MA 02142, USA. Electronic address: shyim@rics.bwh.harvard.edu.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Yim
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Sang-Goo
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Republic of Korea; Department of Animal Life Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Eun Bae
authors.initials: EB
authors.lastname: Kim
authors.affiliation: The National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon, Chungbuk 363-883, Republic of Korea.
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.affiliation: The National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon, Chungbuk 363-883, Republic of Korea.
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Chang
authors.affiliation: Department of Physiology and The Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, USA.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Buffenstein
authors.affiliation: Department of Physiology and The Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, USA.
authors.forename: Kaitlyn N
authors.initials: KN
authors.lastname: Lewis
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Park
authors.affiliation: Department of Pathology and Geriatrics Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Miller
authors.affiliation: Broad Institute, Cambridge, MA 02142, USA. Electronic address: clary@broadinstitute.org.
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute, Cambridge, MA 02142, USA. Electronic address: vgladyshev@rics.bwh.harvard.edu.
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D008322:Mammals / Q000378:metabolism*; D055442:Metabolome / Q000502:physiology*; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D013045:Species Specificity