Format

Send to

Choose Destination
PLoS One. 2017 Feb 15;12(2):e0166875. doi: 10.1371/journal.pone.0166875. eCollection 2017.

The use of urinary proteomics in the assessment of suitability of mouse models for ageing.

Author information

1
Mosaiques Diagnostics GmbH, Hannover, Germany.
2
Hannover Medical School, Core Facility Proteomics, Hannover, Germany.
3
Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.
4
Université Toulouse III Paul-Sabatier, Toulouse, France.
5
Leibniz Institute of Age Research, Fritz Lipmann Institute, Jena, Germany.
6
Inserm-UMR Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
7
Biotechnology Division, Biomedical Research Foundation Academy of Athens, Athens, Greece.
8
Systems Biology of the Cellular Microenvironment Group, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University, Freiburg im Breisgau, Germany.
9
German Cancer Consortium (DKTK), Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
10
University Hospital Freiburg, Freiburg, Germany.
11
Department of Medicine IV, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.
12
BIOSS Center for Biological Signalling Studies, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
13
Center for Systems Biology (ZBSA) and Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs-University Freiburg, Freiburg, Germany.
14
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.

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.

PMID:
28199320
PMCID:
PMC5310860
DOI:
10.1371/journal.pone.0166875
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center