Effects of Lifelong Aerobic Exercise on Ferroptosis-Related Gene Expressions in Kidney of Aged Mice

PURPOSE This study sought to explore the impact of continuous aerobic exercise throughout life on the expression of ferroptosis-related genes in aging kidneys, elucidating the role of exercise in maintaining kidney health. METHODS Male C57BL/6 mice were divided into young control, young exercise, old control, and old exercise groups, with the latter providing access to spontaneous running wheels. Aged mice were observed until 99 weeks, while young mice were followed until 22 weeks. Kidney tissue samples underwent analysis through quantitative polymerase chain reaction, iron assays, histological staining, and pathological damage scoring. RESULTS Expression of Nphs1 and Nphs2 exhibited no significant changes after exercise. However, histological analysis revealed that age-related kidney damage, including glomerular mesangial proliferation, was notably offset by lifelong aerobic exercise. The expression of Slc7a11 and Gpx4 remained unaffected by exercise, whereas Nfe2l2 expression decreased significantly in the young exercise groups. Acsl4 expression exhibited no aging - or exercise-induced differences. Additionally, Tfrc expression was lower in the young exercise group than in the young control group but remained consistent between the old and old-exercise groups. Total iron (Fe) increased in aged mice compared to that in the young-exercise group, and the Fe2+/Total Fe ratio was lower in the old-exercise than in the old control group. CONCLUSIONS Lifelong aerobic exercise positively impacted kidney health by enhancing antioxidant capacity and mitigating iron accumulation. These findings underscore the significance of exercise in preventing age-related deterioration in kidney function.