The biological phosphate regulatory system plays an important role in longevity and aging. Recent work focusing on the aging suppressor gene Klotho suggests that “phosphate accelerates aging”, thereby directing the focus toward various diseases caused by an abnormal phosphate balance mediated by the fibroblast growth factor 23 (FGF23) /Klotho/Vitamin D axis. In the present study, using knock-out mice and cultured cells, we revealed that the FGF23/Klotho/Vitamin D axis mediates mineral homeostasis from early development to late adulthood. Our findings suggest that the biological vitamin D status in chronic diseases can control aging. Analysis of methods to suppress aging by modifying phosphate and vitamin D metabolism in association with the prevention or improvement of progressive chronic kidney disease or cerebral dysfunction could help to promote a healthy life and slow the aging process through a nutritional approach.