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

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

MeSH terms

  • Aging / urine*
  • Animals
  • Capillary Electrochromatography
  • Female
  • Humans
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Knockout
  • Models, Biological*
  • Peptides / urine*
  • Proteome / metabolism*
  • Proteomics*

Substances

  • Peptides
  • Proteome

Grant support

The project was partly funded by grant GA 31354 (CodeAge) FP7-PEOPLE-2011-ITN program (to HM and ENK), BMBF Gerontosys II project (NephAge, 031 5896A) (to PZ, MB, WBW and TBH), by a Marie Curie EU grant (CIG 293568) (to WBW), by the Margarete von Wrangell Habilitationsprogramm, (Ministerium für Wissenschaft Baden-Württemberg) (to WBW), by the Mathilde-Wagner-Habilitationspreis (to WBW), by the German Research Foundation (DFG): CRC 992 (to TBH) and Heisenberg program (to TBH), by the European Research Council-ERC grant 616891 (to TBH); by the BMBF-STOP-FSGS 01GM1518C (to TBH), and by the Excellence Initiative of the German Federal and State Governments (EXC294, BIOSS II to TBH). The funders provided support in the form of salaries for authors [ENK, SB, MP, TK, MB, WBW, TBH, KLR, HM and PZ], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.