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

被引:218
作者
Mitnitski, Arnold [1 ]
Collerton, Joanna [2 ,3 ]
Martin-Ruiz, Carmen [3 ,4 ]
Jagger, Carol [2 ,3 ]
von Zglinicki, Thomas [3 ,5 ]
Rockwood, Kenneth [6 ]
Kirkwood, Thomas B. L. [3 ,5 ]
机构
[1] Dalhousie Univ, Dept Med, Halifax, NS B3H 2E1, Canada
[2] Inst Hlth & Soc, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England
[3] Newcastle Univ, Inst Ageing, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England
[4] Inst Neurosci, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England
[5] Inst Cell & Mol Biosci, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England
[6] Dalhousie Univ, Div Geriatr Med, Halifax, NS B3H 2E1, Canada
基金
英国医学研究理事会; 加拿大健康研究院; 英国生物技术与生命科学研究理事会;
关键词
Ageing; Biomarkers; Cellular ageing; Deficit accumulation; Frailty; Frailty index; Frailty phenotype; Immunosenescence; Inflammation; Newcastle 85+study; DEFICIT ACCUMULATION; OLDER-ADULTS; TELOMERE LENGTH; RISK-FACTORS; INDEX; MORTALITY; HEALTH; CHINESE; PEOPLE; DISEASE;
D O I
10.1186/s12916-015-0400-x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页数:9
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