Sarcopenia is a common disorder that leads to a progressive decrease in skeletal muscle function in elderly people. Exercise effectively prevents or delays the onset and progression of sarcopenia. However, the molecular mechanisms underlying how exercise intervention improves skeletal muscle atrophy remain unclear. In this study, we found that 21‐month‐old zebrafish had a decreased swimming ability, reduced muscle fibre cross‐sectional area, unbalanced protein synthesis, and degradation, increased oxidative stress, and mitochondrial dysfunction, which suggests zebrafish are a valuable model for sarcopenia. Eight weeks of exercise intervention attenuated these pathological changes in sarcopenia zebrafish. Moreover, the effects of exercise on mitochondrial dysfunction were associated with the activation of the AMPK/SIRT1/PGC‐1α axis and 15‐PGDH downregulation. Our results reveal potential therapeutic targets and indicators to treat age‐related sarcopenia using exercise intervention. Exercise reduce zebrafish sarcopenia may by activating the AMPK/SIRT1/PGC‐1α axis and down‐regulating 15‐PGDH to improve mitochondrial function. Aging induces oxidative stress and mitochondrial dysfunction in skeletal muscle, reducing myofibre cross‐sectional area, imbalance in protein synthesis and degradation, and, ultimately, muscle atrophy. Exercise inhibited oxidative stress and improved mitochondrial function may via AMPK/SIRT1/PGC‐1α axis activation and 15‐PGDH downregulation, effectively preventing age‐related sarcopenia (Created with BioRender.com.).