A Regulatory Attractor Model of Evolutionarily Conserved Cellular Autonomy, Pathological State Propagation, and Chronic Disease Progression

Abstract Current biomedical paradigms explain cancer, chronic inflammatory disorders, persistent infections, degenerative diseases, and regenerative phenomena primarily through disease-specific molecular mechanisms. Although these approaches have generated major advances, diverse biological systems repeatedly converge on remarkably similar adaptive behaviors including survival optimization, resistance to elimination, metabolic reprogramming, signaling plasticity, environmental responsiveness, and long-term persistence. NOAH6 proposes a systems-level framework that interprets these observations through a common regulatory principle: the balance between organism-level regulation and cellular-level autonomy. The framework introduces the concept of an Autonomous Program, defined as a distributed architecture of evolutionarily conserved survival, morphogenetic, and persistence modules inherited from unicellular ancestors and retained throughout multicellular evolution. Under physiological conditions these modules remain subordinated to higher-order regulatory systems including neural, endocrine, immune, metabolic, epigenetic, and tissue-level control mechanisms. NOAH6 further proposes that chronic regulatory stress may progressively displace homeostatic thresholds and stabilize a pathological attractor designated Pₛtate. Within Pₛtate, regulatory flexibility decreases while autonomous biological behavior becomes increasingly expressed. The framework introduces a novel concept termed Propagation of Pathological Regulatory States, proposing that disease progression may involve transmission of pathological regulatory information in addition to propagation of pathological cells. To facilitate empirical investigation, the model introduces: • the Autonomy Signature, • the Pₛtate Index, • an attractor-based mathematical formulation, • a hierarchical execution framework linking ROS signaling, calcium signaling, VGCC pathways, α2δ-associated regulation, and CLIC1 activation. Cancer, regenerative plasticity, xenobots, anthrobots, parasitic persistence, and selected aspects of viral exploitation are interpreted as manifestations of a common Regulation–Autonomy continuum. The framework generates experimentally testable predictions and proposes a roadmap for computational, cellular, organoid, animal, and human validation.