The Emerging Role of Water Loss in Dog Aging.

Aging involves progressive physiological changes, including the dysregulation of water homeostasis, essential for cellular function, neuronal signaling, and musculoskeletal integrity. This review explores the emerging role of water loss as a central and underestimated driver of functional decline in aging, with a focus on the dog, both as a clinically relevant target species and as a model for human aging. Age-related alterations in water metabolism-driven by changes in body composition, aquaporin (AQP) expression, electrolyte imbalances, reduced thirst perception, and impaired urine concentration-lead to intracellular and extracellular dehydration, exacerbating functional decline. We examine molecular mechanisms of water regulation involving AQPs and osmolytes, and describe how dehydration contributes to structural and metabolic dysfunction across key biological compartments, including the kidney, brain, bone, and skeletal muscle. Physiological dehydration, a hallmark of aging, intensifies inflammaging, accelerating tissue degeneration. In particular, we highlight how water loss impairs solvent capacity, solute transport, protein conformation, and cellular communication. Despite the known role of macronutrients in geriatric nutrition, hydration remains an often-overlooked factor in aging management. We argue for its inclusion as a fourth pillar in the nutritional approach to veterinary geriatrics, alongside protein, fat, and fiber. By investigating aging-associated water loss in dogs-species that share environments and lifestyle patterns with humans-we propose hydration-centered strategies to promote healthy aging in both veterinary and comparative medicine.