In a mouse model of cerebral ischemia, voluntary wheel running increased myokine irisin; irisin, in turn, upregulated the longevity protein Klotho, permitting nuclear FoxO3a accumulation and MnSOD transcription, thereby quenching reactive oxygen species and improving cognition (Jin et al., 2021). The gene discussed is FNDC5; the disease is Cerebral ischemia.