Do blood ageing markers predict death better as a bundle than one-by-one?
In 777 Newcastle 85+ participants, a 40-biomarker frailty index predicted 7-year mortality (HR 1.05 per 1% FI-B; AUC 0.66) better than any single marker (AUC ≤0.61); combining with the clinical FI raised AUC to 0.75.
Source
Age-related frailty and its association with biological markers of ageing
Study at a glance
- Design
- Cohort — Newcastle 85+ cohort: baseline biomarker/clinical frailty indices vs up to 7-year mortality.
- N
- N=845 · 845 enrolled (mean age 85.5); FI-B calculable in 777 (60.9% women).
- Population
- Very old adults in the Newcastle 85+ Study (UK), mean age 85.5 years.
- Outcome
- All-cause mortality predicted by a 40-item biomarker frailty index (FI-B) vs clinical FI-CD, Fried phenotype, and single biomarkers.
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Do blood ageing markers predict death better as a bundle than one-by-one?
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Newcastle 85+ analytic frame was n=845, mean age 85.5; FI-B in 777.
We analyzed baseline data and up to 7-year mortality in the Newcastle 85+ Study (n = 845; mean age 85.5).
Mean FI-B was 0.35 vs FI-CD 0.22; each 1% FI-B raised HR by 5.4%.
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.
What they did
Built FI-B from 40 cellular-ageing, inflammation, haematology, and immunosenescence markers, compared it with a clinical deficit FI and the Fried phenotype, and tested 7-year mortality with Cox models, Kaplan–Meier strata, random biomarker subsamples, and ROC AUCs.
What they found
Mean FI-B 0.35 vs FI-CD 0.22; nobody had FI-B <0.12. Each 1% FI-B rise raised HR by 5.4%. FI-B beat every individual biomarker and was robust to dropping items. Combined FI-CD/FI-B AUC was 0.75 vs 0.71 and 0.66 alone.
The limits
What it doesn't show
Moderate AUCs are not bedside tests; FI-B and FI-CD correlated only weakly (r=0.16), so blood markers do not simply duplicate clinical frailty.
Key terms
- FI-B
- Biomarker frailty index: proportion of 40 laboratory ageing deficits present (mean 0.35).
- FI-CD
- Clinical-deficits frailty index (mean 0.22) based on health problems, not labs.
- Fried phenotype
- Classic five-item physical frailty phenotype used as a comparator.
- Newcastle 85+ Study
- UK cohort of people around age 85; n=845 here with up to 7-year mortality.
- Deficit accumulation
- Frailty as the ratio of deficits present to deficits counted—applied here to blood markers.
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Newcastle 85+ n in the methods was:
Common questions
How old were participants?
Mean 85.5 years; FI-B n=777, 60.9% women.
Mean FI-B vs FI-CD?
0.35 vs 0.22; no one had FI-B <0.12.
Mortality HR per 1% FI-B?
About 1.05 (5.4% higher hazard).
Best discrimination?
Combined FI-CD + FI-B AUC 0.75 for 7-year death.
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