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. Overall design: To explore the effects of Ex on brain aging, and to investigate whether and how Ex induces changes in molecular and spatial signatures of aging across the brain.

衰老会引发认知能力的渐进性衰退，而运动（Exercise, Ex）或可延缓这一进程。目前学界对于运动是否能够诱导全脑衰老的分子与空间特征发生改变，以及其具体调控机制仍不甚明晰。
本研究评估了运动对抗认知衰老的效果，并以单细胞核分辨率（single-nuclei resolution）对全脑在衰老状态及运动干预下的分子与空间特征变化进行了系统表征。
整体实验结果显示，运动为老年小鼠带来了显著的认知益处，并在很大程度上保护脑细胞免受衰老损伤，其中对神经元的保护作用尤为突出。运动调控了抑制性神经元特异性的衰老相关基因Alcam、Cacna2d3与Foxp2的表达，并重塑了衰老大脑内细胞的空间分布模式，上述变化或共同助力老年小鼠认知功能的年轻化恢复。
本研究为解析运动对抗脑衰老的有益作用机制提供了极具价值的科学见解。
研究设计概述：本研究旨在探究运动对脑衰老的调控作用，并明确运动是否能够诱导全脑衰老的分子与空间特征发生改变及其具体作用机制。