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

摘要

Background: 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. Methods: 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 spectro-metry, 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. Results: 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. Conclusions: 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.