The Tissue Coherence Index emerged as a stable and monotonic measure of propagation competence in a computational twin, establishing a falsifiable framework for testing multicellular context propagation.
Introduces the Tissue Coherence Index and a computational framework to test whether impaired multicellular context propagation contributes to aging-like tissue dysfunction.
The Coherence Threshold Hypothesis of Aging proposes that aging may partially reflect a progressive loss of tissue-level context propagation capacity rather than solely molecular damage accumulation. This paper introduces the Tissue Coherence Index (TCI), a quantitative metric designed to measure the total coherent propagation of localized perturbations relative to background noise in multicellular systems. A computational twin using a noisy two-dimensional excitable-cell lattice was developed and iteratively stress-tested through four falsification cycles. The model explored how reduced coupling, elevated stochastic noise, and prolonged recovery dynamics influence multicellular propagation behavior. Across robustness tests, TCI emerged as a stable and monotonic measure of propagation competence, while several intuitive spatial metrics failed under realistic noise conditions. The paper further presents a complete wet-lab experimental protocol and Colab-ready analysis pipeline for testing TCI in cultured biological systems using calcium or voltage imaging. Explicit falsification criteria, rescue interventions, and metric failure analyses are included. This work does not claim proof of a universal aging mechanism. Rather, it establishes a falsifiable systems-level framework for experimentally testing whether impaired multicellular context propagation contributes to aging-like tissue dysfunction.
Thomas S. Mitchell (Tue,) conducted a other in Aging. Tissue Coherence Index (TCI) was evaluated on Total coherent propagation of localized perturbations relative to background noise. The Tissue Coherence Index emerged as a stable and monotonic measure of propagation competence in a computational twin, establishing a falsifiable framework for testing multicellular context propagation.