Exercise alters the single-nuclei and spatial transcriptional profiles of mouse aging brain

Aging drives a progressive decline in cognition that may be delayed by exercise (Ex). Whether and how Ex induces changes in molecular and spatial signatures of aging across the brain remains little known. Herein, we assessed the effects of Ex against cognitive aging, and characterized the molecular and spatial changes by aging and upon Ex across the brain at the single-nuclei resolution. Overall, Ex demonstrated cognitive benefits in old mice and largely protected the brain cells against aging, especially the neurons. Ex regulated the inhibitory neuron-specific aging-associated genes Alcam, Cacna2d3, and Foxp2, and reorganized the spatial distribution of cells across the aging brain, which may collectively contribute to the rejuvenation of cognitive function in aged mice. This study provides invaluable insights into Ex-induced benefits against brain aging. To explore the effects of Ex on brain aging, particularly cognitive aging, and to investigate whether and how Ex induces changes in molecular and spatial signatures of aging across the brain.