title: The use of urinary proteomics in the assessment of suitability of mouse models for ageing.
abstract: Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8-96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing.
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.|Hannover Medical School, Core Facility Proteomics, Hannover, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Nkuipou-Kenfack
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.affiliation: Leibniz Institute of Age Research, Fritz Lipmann Institute, Jena, Germany.
authors.forename: Seerat
authors.initials: S
authors.lastname: Bajwa
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Pejchinovski
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Vinel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Dray
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.affiliation: Inserm-UMR Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Bascands
authors.affiliation: Biotechnology Division, Biomedical Research Foundation Academy of Athens, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Vlahou
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Koeck
authors.affiliation: Systems Biology of the Cellular Microenvironment Group, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University, Freiburg im Breisgau, Germany.|German Cancer Consortium (DKTK), Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Borries
authors.affiliation: Systems Biology of the Cellular Microenvironment Group, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University, Freiburg im Breisgau, Germany.|German Cancer Consortium (DKTK), Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Busch
authors.affiliation: University Hospital Freiburg, Freiburg, Germany.
authors.forename: Wibke
authors.initials: W
authors.lastname: Bechtel-Walz
authors.affiliation: Department of Medicine IV, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.|BIOSS Center for Biological Signalling Studies, Albert-Ludwigs-University Freiburg, Freiburg, Germany.|Center for Systems Biology (ZBSA) and Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs-University Freiburg, Freiburg, Germany.
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Huber
authors.affiliation: Leibniz Institute of Age Research, Fritz Lipmann Institute, Jena, Germany.
authors.forename: Karl L
authors.initials: KL
authors.lastname: Rudolph
authors.affiliation: Hannover Medical School, Core Facility Proteomics, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pich
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.|BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Zürbig
mesh_terms: D000375:Aging / Q000652:urine*; D000818:Animals; D053801:Capillary Electrochromatography; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010455:Peptides / Q000652:urine*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics
chemical_list: D010455:Peptides; D020543:Proteome