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Proteomic studies reveal that training is associated with mitochondrial metabolism, extracellular matrix remodeling, and muscle contractile protein abundance, reducing proteostatic dysfunction. Metabolomic analyses demonstrate that exercise improves metabolic flexibility and remodels cellular energy networks. Importantly, the unique contribution of this review lies in synthesizing emerging evidence that these adaptations are highly cell- and tissue-specific, involving immune cells, skeletal muscle satellite cells, endothelial cells, microglia, and intestinal stem cells. 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