Estradiol supplementation therapy has been shown to reduce extracellular matrix precipitation in glomerular and mesangial cells of diabetic animals, protect podocytes from damage, ameliorate age-related glomerular hypertrophy, increase nitric oxide (NO) production, and regulate vascular endothelial growth factor (VEGF) expression in tubular and vascular smooth muscle cells. The gene discussed is VEGFA; the disease is age.