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Licensed Unlicensed Requires Authentication Published by De Gruyter February 28, 2019

Post-translational modification-derived products are associated with frailty status in elderly subjects

  • Rachid Mahmoudi EMAIL logo , Stéphane Jaisson , Sarah Badr , Yacine Jaidi , Laurie-Anne Bertholon , Jean-Luc Novella and Philippe Gillery



Identifying frail elderly subjects is of paramount importance in order to conduct a tailored care. The characterization of frailty status is currently based on the collection of clinical data and on the use of various tools such as Fried’s criteria, which constitutes a difficult and time-consuming process. Up to now, no biological markers have been described as reliable tools for frailty characterization. We tested the hypothesis that a link between frailty and protein molecular aging existed. This study aimed therefore at determining whether post-translational modification derived products (PTMDPs), recognized as biomarkers of protein aging, were associated with frailty status in elderly subjects.


Frailty status was determined according to Fried’s criteria in 250 elderly patients (>65 years old) hospitalized in a short-term care unit. Serum concentrations of protein-bound PTMDPs, including carboxymethyllysine (CML), pentosidine, methylglyoxal-hydroimidazolone-1 and homocitrulline (HCit), were determined by liquid chromatography coupled with tandem mass spectrometry, and tissue content of advanced glycation end-products was assessed by skin autofluorescence (SAF) measurement. Associations between PTMDPs and frailty status were analyzed using logistic regression models.


Frail patients had significantly (p<0.01) higher CML, HCit, and SAF values compared to non-frail and pre-frail subjects. By multivariate analysis, only HCit concentrations and SAF values remained associated with frailty status (p=0.016 and p=0.002, respectively), independently of age, comorbidities, renal function, C-reactive protein and albumin concentrations.


HCit and SAF are significantly associated with frailty status in elderly subjects. This study suggests that PTMDPs constitute promising biomarkers for identifying frail patients and guiding personalized patient care.

Corresponding author: Prof. Rachid Mahmoudi, MD, PhD, University Hospital of Reims, Department of Internal Medicine and Geriatrics, Maison Blanche Hospital, 45 rue Cognacq-Jay, 51092 Reims cedex, France; and University of Reims Champagne-Ardenne, Faculty of Medicine, EA 3797, Reims, France, Phone: + 33 3 26 83 23 41, Fax: + 33 3 26 78 42 28, Phone: + 33 3 26 83 23 41, Fax: + 33 3 26 78 42 28
aRachid Mahmoudi and Stéphane Jaisson contributed equally to this work.


The authors thank all the participants of this study, the staff of the Department of Internal Medicine and Geriatrics, the staff of the Department of Biochemistry of Reims University Hospital, and especially Mrs. Tatiana Decampos Dos Santos and Isabelle Flandre.

  1. Author contributions: All the authors contributed significantly to the study (conception, design, and interpretation of the data, critical revision of the manuscript for important intellectual content, and approval of the final version). In addition, Rachid Mahmoudi, Stephane Jaisson, and Philippe Gillery contributed to the analysis strategy and wrote the article.

  2. Research funding: This study was funded by the University of Reims Champagne-Ardenne and the Reims University Hospital through the “Projet Hospitalo Universitaire VIeillissement protéique et VAsculaire (PHU-VIVA)” program.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2018-12-12
Accepted: 2019-02-06
Published Online: 2019-02-28
Published in Print: 2019-07-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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