We hypothesize that aerobic exercise, in addition to being an impressive Klotho upregulator, inhibite the TGF-β1/Smad3 and Wnt/β-linker protein signaling pathways, forming a delayed benign feedback loop with TGF-β1/p53/miR-34a in renal fibrosis. This evidence concerns the gene SMAD3 and renal fibrosis.