AI Insight
This study introduces a framework for quantifying predictive uncertainty in biological age estimates, revealing that traditional age-gap measurements can be misleading when predictions vary in reliability. Applying this approach to UK Biobank data with multiple biological age clocks, researchers found that predictive uncertainty itself was independently associated with disease risk and mortality, particularly for composite, brain, and immune system clocks. The findings suggest that uncertainty in biological age predictions captures an additional dimension of aging beyond simple age acceleration, potentially reflecting molecular heterogeneity and dysregulation.
Why it matters
This framework enables more accurate individual-level risk assessment by distinguishing between reliable and unreliable biological age predictions, which could improve disease prevention strategies and personalized monitoring. The discovery that prediction uncertainty independently predicts health outcomes suggests clinicians should consider not just whether someone appears biologically older, but also how confident that assessment is.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Biological age estimates are increasingly used to study aging, disease risk, and mortality, yet their predictive uncertainty is rarely quantified. Consequently, conventional age-gap measures can treat deviations as equally informative even when the underlying biological age predictions differ substantially in reliability. We developed a framework for uncertainty-aware biological aging that generates calibrated prediction intervals and individualized probabilities of accelerated or decelerated aging alongside point estimates. We applied this framework to the UK Biobank Pharma Proteomics Project, evaluating three composite and eleven organ-specific biological age clocks. Predictive uncertainty varied substantially both within and across clocks, revealing that apparently extreme age gaps can differ markedly in the strength of evidence supporting accelerated or decelerated aging. In particular, low-accuracy clocks, including many organ-specific clocks, provided little evidence for confidently accelerated or decelerated aging. Beyond biological age gaps, prediction-interval width was independently associated with disease risk and mortality, particularly for composite, brain, and immune clocks, suggesting that predictive uncertainty captures an additional dimension of biological aging that may reflect increased molecular heterogeneity and dysregulation associated with aging and disease. We replicated these findings in Biobank Japan and an independent clinical cohort from Stanford. By incorporating individual-specific predictive uncertainty, our framework provides a more informative characterization of biological aging and enables improved individual-level risk stratification for disease prevention and longitudinal monitoring.