Coherence, transformation, and breakdown in living systems: part II - predictions and implications for systemic health.

Authors

Andreas Nicolaides

Published in

Frontiers in systems biology. Volume 6. Pages 1910994. Epub Oct 14, 2026.

Abstract

Part I of this two-part series advanced the CHORA Hypothesis as a candidate account of biological coherence: how organised biological function is sustained, transformed, and lost within the organism and across the lineage over deep time. The hypothesis holds that a Common Higher-Order Regulatory Architecture (CHORA) operates as an integrated, hierarchically structured level of organisation across cells, tissues, organisms, and generations, sustaining within-organism coherence and evolutionary coherence alike. It holds further that the germline is the principal conduit through which the architecture is propagated, that the same architectural features which sustain biological coherence underlie the characteristic modes of its failure, and that disruption of the architecture at the organism level underlies the convergent signatures of systemic disease. This paper develops the empirical predictions and the systemic health implications that follow. Section 1 sets out six predictions under the commitments from which they follow. The first three follow from the architecture's integrated operation: catastrophic rather than graded failure at architecturally central components; the concentration of lineage transitions at mid-hierarchical regulatory levels; and the bidirectional intergenerational consequences of perturbation at germline-soma coupled components. The fourth derives from germline priority in propagation and concerns intergenerational erosion under partial germline compromise, with somatic analogues at architecturally shared components. The fifth derives from the coherence-breakdown relationship and concerns the entrenchment of pathological regimes through feedback architectures repurposed under displaced upstream conditions. The sixth derives from disruption of the architecture at the organism level and concerns the convergence of systemic pathologies on shared signatures of architectural breakdown. Each prediction is examined against alternative accounts and the postdictive and prospective evidence bearing on it. Several predictions organise existing evidence under a single architectural account; others are mainly prospective. Section 2 draws out the implications for systemic health. Health and entrenched systemic disease are not opposing states but alternative regimes of the same biological-coherence-sustaining architecture. On this account, developmental origins, ageing, and intergenerational transmission are intelligible as expressions of a shared architectural logic. The deeper ontological question of what kind of thing this architecture is, together with the framework's broader conceptual implications, is addressed in a forthcoming publication.

PMID:
42952520
Bibliographic data and abstract were imported from PubMed on 29 Oct 2026.

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