A Blood Homeostatic State Space for Immune Ageing: Persistence Gain, Reserve Loss, and Constrained Longitudinal Dynamics

Blood is often used either as a source of individual biomarkers or as input for scalar immune-age and biological-age models. This study tests a different question: whether blood-derived longitudinal measurements can be represented as a structured homeostatic state space. A rebuilt blood HRSM framework was applied to a primary repeated-measures IMM-AGE cellular object and to supporting transcriptomic blood branches. The state vector was defined by reserve-like support, trajectory recoverability, coherence or volatility control, and retained persistence. In the primary IMM-AGE object, published immune age aligned strongly with higher retained persistence, lower reserve-like support, and lower coherence, while recoverability was weak. The strongest single cellular driver was naive CD8⁺ T-cell decline, consistent with established immune-ageing biology. Longitudinal tests showed that temporal memory was strongest in the persistence axis, with reserve-like support moving in the opposite direction. A subject-level persistence index indicated stronger preservation of the 2008 blood-state configuration in younger baseline subjects. Joint HRSM entropy declined across time, suggesting compression of the accessible multivariate blood-state distribution. Sensitivity checks preserved the central ageing polarity after removal of PD1 from the persistence map, use of a reduced core map, and removal of broad lymphocyte-bulk support terms. Supporting GSE213313 analyses provided a completed transcriptomic blood branch with negative controls, comparators, and cross-dataset validation against GSE324831. Cross-dataset portability was strongest for support, recoverability, and coherence families, whereas persistence was not portable as a fixed molecular family and was better interpreted as a context-sensitive behaviour. The results support blood HRSM as a systemic gateway representation of immune ageing, not as a replacement for existing immune-age clocks and not as a universal molecular-memory claim.