Biological systems exhibit adaptive plasticity under perturbation, yet recovery after restoration of baseline conditions is frequently incomplete. We propose the Epigenetic Regulation State-Space (ERSS) (formerly named as the Epigenetic Homeostasis Theory), a conceptual systems-level framework describing the coupling between energetic coordination and structural epigenetic constraint. ERSS formalizes biological irreversibility as a history-dependent state-space phenomenon rather than a purely molecular defect. We introduce three axioms, ten organizing principles, and derived corollaries that generate falsifiable predictions. This framework does not propose new molecular actors, but reorganizes established biological modules into a coherent structure that permits decisive experimental testing of reversibility limits.
Anh Hao Bui (2026) studied this question.