8. Current Biomarkers of Aging Remain Limited in Accuracy, Coverage, and Causal Interpretability

Current biomarkers exhibit insufficient accuracy and reproducibility when applied to individuals, due to single omic projections, sampling (often blood-centric), resolution (bulk mixtures mask cell-state shifts), costs, unclear causality, and interpretability. They also do not measure the deleteriome, instead measuring broader changes. The clocks also depend on reference populations: a clock trained in one cohort can mis-calibrate in another due to ancestry, environment, comorbidities, or technical differences. Progress will come from integrating multi-modality, organ-specific readouts, and causal frameworks; from designing benchmarks that require clocks to predict interventions and outcomes, not just age; and from doing so in many populations.