Multimorbidity and animal models.

Multimorbidity-the co-occurrence of more than two chronic conditions in the same individual-is associated with premature death, diminished function, reduced quality of life, and increased societal burden. This complex state involves dynamic interactions across multiple conditions, organ systems, and physiological pathways; yet research progress remains constrained by inadequate animal models that recapitulate human complexity. This review summarizes the predominant patterns of multimorbidity and evaluates current animal models spanning invertebrates, rodents, and large mammals. While no single model fully captures the multifaceted nature of human multimorbidity, we propose several strategic directions to address existing limitations: implementing a cross-species validation framework (from simple organisms to rodents to large mammals), standardizing protocols integrating multimodal risk factors, developing advanced non-animal models, and enhancing ethical oversight. Advancing multimorbidity models is crucial for decoding disease interactions and accelerating translation of research findings into improved patients outcomes.