Decoding exercise-induced delayed aging from a single-cell perspective

Aging is a systematic process characterized by the functional decline of multiple organs such as skeletal muscle, the nervous system, and the cardiovascular system. Age-related conditions such as sarcopenia, neurodegenerative diseases, and vascular dysfunction have become major health challenges in aging societies. Regular physical activity, a safe and effective non-pharmacological intervention, has been extensively demonstrated to ameliorate aging-related phenotypes across these systems. Recent advances in single-cell omics technologies provides an unprecedented tool to dissect the precise cellular regulatory networks underlying exercise interventions. This review systematically summarizes the recent progress in applying single-cell omics to decode how exercise delays multi-organ and systemic aging. Findings reveal that the aging process exhibits significant cellular heterogeneity, which is manifested by abnormal function of muscle stem cells, neural precursor cells, and specific endothelial cell subsets, accompanied by the formation of a chronic inflammatory microenvironment and dysregulation of intercellular communication networks. Exercise exerts its anti-aging effects by remodeling the immune landscape, repairing stem cell niches, and regulating key signaling pathways including notch, transforming growth factor-beta, and myokines networks. In summary, single-cell omics has enabled preliminary mapping of the spatiotemporal molecular networks and cellular heterogeneity through which exercise delays multisystem aging, offering a new paradigm for interventions against age-related diseases and revolutionizing our understanding of exercise-mediated aging regulation. These advances lay a solid foundation for the rational design of precision exercise interventions and novel therapeutic strategies to mitigate age-related functional decline and foster healthy aging.