Biological age uncertainty and later health in UK Biobank
In over 450,000 UK Biobank participants, a proposed measure of uncertainty in predicted biological age was linked to later mortality, multimorbidity and loss of healthspan, independently of the age gap itself. [1]
Automatic summary · not editorially reviewed
The key findings
The authors propose a probabilistic framework deriving biological age gap and biological age uncertainty from predicted-age distributions in more than 450,000 UK Biobank participants. [1]
Higher uncertainty was associated with mortality independently of the age gap, with hazard ratios of 1.24 for the NMR-derived and 1.40 for the proteomic-derived measure per standard deviation. [1]
Mortality associations were replicated using a routine-blood-derived measure in three independent external cohorts. [1]
The source at a glance
- Study type / format
- Prospective cohort study with cross-omic and genetic analyses (abstract).
- Population / context
- More than 450,000 UK Biobank participants, plus three independent external cohorts for replication.
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- September 28, 2026
Proposed uncertainty measure in UK Biobank
Biological aging clocks usually compress complex biological profiles into one age estimate. The authors propose a probabilistic framework that derives two values from the mean and width of predicted-age distributions: the biological age gap and biological age uncertainty. They applied it to more than 450,000 UK Biobank participants and then examined later associations with aging-related outcomes. Uncertainty was only weakly correlated with the age gap and rose with disagreement among age signals across individual molecules and discrete organs.
Supporting source [1]
Later mortality and healthspan associations
Higher uncertainty was associated with mortality, loss of healthspan and multimorbidity independently of the age gap. Mortality hazard ratios were 1.24 (95% CI 1.23–1.26) per standard deviation for the NMR-derived measure and 1.40 (95% CI 1.37–1.43) for the proteomic-derived measure. Longitudinal increases in the NMR-derived measure were associated with subsequent health decline, and mortality associations were replicated using a routine-blood-derived measure in three independent external cohorts. These are associations, not evidence that uncertainty causes these outcomes.
Supporting source [1]
Molecular and genetic profiling of uncertainty
Cross-omic analyses linked uncertainty to inflammation, metabolic regulation and tissue remodelling. Genetic analyses showed overlapping but distinct architectures for uncertainty and the age gap, and tissue and functional mapping further implicated immune and lipid-metabolic processes. The authors describe this as a framework for characterizing biological age through both its mean deviation and its uncertainty, and define uncertainty as a new dimension of human aging. The abstract does not report effect sizes for the molecular or genetic analyses, and the full text was not reviewed.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. The abstract reports no effect sizes for the molecular or genetic analyses, and the mortality findings are prospective associations, not causal evidence.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Li Y, Feng G, Yan S, Huang Q, Jiang J, Pei Z, Tay LX, Li K, Pan Z, Yuan Z, Gao L, Ji JS, Ke L, Gu K, Di Q. · europepmc.org · September 28, 2026