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Age-related frailty and its association with biological markers of ageing

Lookup NU author(s): Dr Joanna Collerton, Dr Carmen Martin-RuizORCiD, Emerita Professor Carol Jagger, Professor Thomas von Zglinicki, Emeritus Professor Thomas Kirkwood



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: The relationship between age-related frailty and the underlying processes that drive changes in health is currently unclear. Considered individually, most blood biomarkers show only weak relationships with frailty and ageing. Here, we examined whether a biomarker-based frailty index (FI-B) allowed examination of their collective effect in predicting mortality compared with individual biomarkers, a clinical deficits frailty index (FI-CD), and the Fried frailty phenotype.Methods: We analyzed baseline data and up to 7-year mortality in the Newcastle 85+ Study (n = 845; mean age 85.5). The FI-B combined 40 biomarkers of cellular ageing, inflammation, haematology, and immunosenescence. The Kaplan-Meier estimator was used to stratify participants into FI-B risk strata. Stability of the risk estimates for the FI-B was assessed using iterative, random subsampling of the 40 FI-B items. Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under receiver operating characteristic (ROC) curves.Results: The mean FI-B was 0.35 (SD, 0.08), higher than the mean FI-CD (0.22; SD, 0.12); no participant had an FI-B score <0.12. Higher values of each FI were associated with higher mortality risk. In a sex-adjusted model, each one percent increase in the FI-B increased the hazard ratio by 5.4 % (HR, 1.05; CI, 1.04-1.06). The FI-B was more powerful for mortality prediction than any individual biomarker and was robust to biomarker substitution. The ROC analysis showed moderate discriminative ability for 7-year mortality (AUC for FI-CD = 0.71 and AUC for FI-B = 0.66). No individual biomarker's AUC exceeded 0.61. The AUC for combined FI-CD/FI-B was 0.75.Conclusions: Many biological processes are implicated in ageing. The systemic effects of these processes can be elucidated using the frailty index approach, which showed here that subclinical deficits increased the risk of death. In the future, blood biomarkers may indicate the nature of the underlying causal deficits leading to age-related frailty, thereby helping to expose targets for early preventative interventions.

Publication metadata

Author(s): Mitnitski A, Collerton J, Martin-Ruiz C, Jagger C, von Zglinicki T, Rockwood K, Kirkwood TBL

Publication type: Article

Publication status: Published

Journal: BMC Medicine

Year: 2015

Volume: 13

Online publication date: 13/07/2015

Acceptance date: 12/06/2015

Date deposited: 02/10/2015

ISSN (electronic): 1741-7015

Publisher: BioMed Central Ltd


DOI: 10.1186/s12916-015-0400-x


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Funder referenceFunder name
Dunhill Medical Trust
Newcastle University
UK Medical Research Council
NIHR Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust
G0601333Biotechnology and Biological Sciences Research Council
G0500997Biotechnology and Biological Sciences Research Council
MOP25388Canadian Institutes of Health Research