Biological age uncertainty independently predicts mortality and health decline in humans

In more than 450,000 UK Biobank participants, researchers developed a probabilistic framework to measure biological age uncertainty alongside the standard biological age gap. Uncertainty correlated weakly with the biological age gap and increased when age signals disagreed across discrete organs and individual molecules. Higher biological age uncertainty independently predicted mortality, loss of healthspan, and multimorbidity. Specifically, mortality hazard ratios were 1.24 per standard deviation for NMR-derived uncertainty and 1.40 for proteomic-derived uncertainty. Longitudinal increases in NMR-derived uncertainty marked subsequent health decline, and routine blood markers replicated mortality findings across three external cohorts. Cross-omic and genetic analyses linked uncertainty to inflammation, lipid metabolism, and tissue remodeling.