The pro-aging effects of endocrine GH/IGF-1 deficiency may be exacerbated by an age-related decline in other vasculoprotective growth factors, including pituitary adenylate cyclase-activating polypeptide (PACAP) (202) and vascular endothelial growth factor (VEGF) (203–205) and endothelial resistance to the effects of pro-angiogenic stimuli (206). This evidence concerns the gene IGF1 and hyperinsulinemic hypoglycemia, familial, 4.