6. Age Deviation Should be Interpreted Relative to the Reference Trajectory

Age deviation (also called age acceleration or age gap) is a residual: the difference between measured biological age and what is typical at a given chronological age (11). A positive age gap does not by itself establish a faster aging rate. Interpretation requires context: deviation may reflect true higher damage burden, a specific disease process that the clock is sensitive to, or noise when clock accuracy and reproducibility are low. The reference data on which the model was trained is also important to interpret a residual from that model. Therefore, it is safest to interpret deviation as divergence from the reference trajectory and then ask what component drives it, in which tissue, and whether it predicts meaningful outcomes. For decision-making, the most useful deviation measures are those that are predictive of future outcomes and are robust across platforms.