Exercise-responsive Wnt/β-catenin signaling across metabolic tissues during aging: A narrative review.

Aging is associated with progressive impairment of metabolic resilience, regenerative capacity, and tissue adaptability across multiple organs. Increasing evidence suggests that dysregulation of Wnt/β-catenin signaling contributes to these alterations by disrupting pathways involved in cellular repair, metabolic flexibility, and stress responsiveness. However, the mechanisms through which aging alters Wnt signaling dynamics across metabolic tissues remain incompletely understood. This narrative review examines how aging-associated changes in canonical and noncanonical Wnt signaling influence functional decline in skeletal muscle, adipose tissue, liver, and pancreas. These alterations contribute to sarcopenia, chronic inflammation, insulin resistance, mitochondrial dysfunction, and impaired metabolic adaptation across tissues. The review further discusses how exercise may modulate Wnt/β-catenin signaling through coordinated mechanical, metabolic, and endocrine inputs, thereby supporting tissue remodeling and metabolic homeostasis during aging. Particular emphasis is placed on tissue-specific adaptations, inter-organ communication, and the translational relevance of exercise-responsive Wnt signaling in metabolic aging. Collectively, this review positions Wnt/β-catenin signaling as a dynamic regulator of metabolic adaptation in aging and highlights exercise as a potential strategy to preserve metabolic healthspan and functional resilience.