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

Authors :
Cédric Dray
Philippe Valet
Esther Nkuipou-Kenfack
Joost P. Schanstra
Karl Lenhard Rudolph
Thomas Koeck
Jean-Loup Bascands
Martin Pejchinovski
Harald Mischak
Tobias B. Huber
Hauke Busch
Melanie Börries
Wibke Bechtel-Walz
Andreas Pich
Antonia Vlahou
Petra Zürbig
Claire Vinel
Seerat Bajwa
Source :
PLOS ONE, 12(2):e0166875, PLoS ONE, PLoS ONE, Vol 12, Iss 2, p e0166875 (2017)
Publication Year :
2017
Publisher :
Public Library of Science, 2017.

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.

Details

Language :
English
ISSN :
19326203
Database :
OpenAIRE
Journal :
PLOS ONE, 12(2):e0166875, PLoS ONE, PLoS ONE, Vol 12, Iss 2, p e0166875 (2017)
Accession number :
edsair.doi.dedup.....db6ccde636d93ff8535d27a5538ea821