Physiological homeostasis and pattern memory: testing bidirectional associations in the Zebrafish Lifespan Regeneration Atlas (ZLRA)

Objectives The aim of this study was to test the bidirectional relationship between systemic physiological homeostasis and pattern memory in a large, longitudinal cohort of zebrafish spanning juvenile to senescent stages. Method Data were obtained from the Zebrafish Lifespan Regeneration Atlas (ZLRA), a cohort comprising 12,099 Danio rerio aged 2–36 months, excluding individuals exhibiting overt patterning defects at baseline. Repeated measures of systemic homeostasis were quantified with the Composite Assessment of Systemic Physiology-19 (CASP-19; integrating redox balance, inflammatory tone, metabolic rate and bioelectric set-point). Pattern memory was indexed by immediate and delayed fin-regeneration fidelity following standardized caudal excision, scored morphometrically at 7 and 30 days post-injury. Both variables were assessed nine times over a 16-month interval. Cross-lagged structural equation models were fitted to evaluate bidirectional associations between homeostasis and pattern memory. Results Higher systemic homeostasis scores were consistently associated with higher subsequent immediate and delayed regeneration fidelity at every interval, though effect sizes were modest (standardized β = 0.04–0.07). There was no evidence that superior pattern memory predicted later improvements in systemic homeostasis. Conclusion Elevated physiological homeostasis is associated with preservation of pattern memory across 16 months of the zebrafish lifespan. The data do not support the converse pathway. The absence of an effect from pattern memory to subsequent homeostasis may indicate that such feedback only emerges after clinically relevant regenerative decline. Enhancement of systemic homeostasis could serve as a protective factor for sustaining pattern memory from early adulthood into advanced age.