A single-cell transcriptomic atlas of exercise-induced anti-inflammatory and geroprotective effects across the body

Exercise benefits the whole organism, yet, how tissues across the body orchestrally respond to exercise remains enigmatic. Here, in young and old mice, with or without exercise, and exposed to infectious injury, we characterized the phenotypic and molecular adaptations to a 12-month exercise across 14 tissues/organs at single-cell resolution. Overall, exercise protects tissues from infectious injury, although more effectively in young animals, and benefits aged individuals in terms of inflammaging suppression and tissue rejuvenation, with structural improvement in the central nervous system and systemic vasculature being the most prominent. In vascular endothelial cells, we found that readjusting the rhythmic machinery via the core circadian clock protein BMAL1 delayed senescence and facilitated recovery from infectious damage, recapitulating the beneficial effects of exercise. Our study underscores the effect of exercise in reconstituting the youthful circadian clock network and provides a foundation for further investigating the interplay between exercise, aging, and immune challenges across the whole organism.

运动有益于全身机体，但机体各组织如何协同响应运动这一问题仍有待阐明。本研究以年轻与老年小鼠为对象，设置运动与非运动两组，并施加感染性损伤刺激，以单细胞分辨率对14种组织/器官在12个月运动干预下的表型与分子适应性特征进行了系统表征。整体而言，运动可保护组织免受感染性损伤，尽管该保护效应在年轻个体中更为显著；同时运动可通过抑制炎性衰老（inflammaging）、促进组织复壮，使老年个体获益，其中中枢神经系统与全身血管的结构改善最为突出。在血管内皮细胞中，我们发现通过核心生物钟蛋白BMAL1重塑节律机制，可延缓细胞衰老并促进感染性损伤后的修复，这一效应复现了运动的有益作用。本研究证实了运动可重建青年态生物钟网络，并为进一步探究全身机体中运动、衰老与免疫挑战之间的相互作用提供了研究基础。