Tissue coordination in ageing and disease

Abstract

How cellular and microenvironmental changes are translated into tissue-level decline remains incompletely understood. Here, we view tissue maintenance through the lens of multicellular coordination, defined as the endogenous management of dependencies among component activities. These dependencies are embodied in a tissue's relational state across signalling networks, epigenetic states, cell composition, and extracellular matrix. The different turnover timescales of these substrates may permit system memory and path dependence. We analyse two constraints that may limit coordination and distributed maintenance: self-reference, wherein the maintenance machinery is itself vulnerable to decline, and a sensing bottleneck, which limits the extent to which cells can perceive and represent age-related change. We explore how tissue architecture and renewal shape the consequences of these constraints for coordination, relational state and tissue function. In some cases, coordination may stabilise a pathological state even after removal of the initiating driver, creating a coordination trap. This view may help explain why tissues exhibit different age-related trajectories and suggests that interventions may also need to restore functional tissue coordination.

The authors' abstract, as published at the source. Ageing Research Reviews, 2026 · DOI ↗