Kotho and aging.
Three fibroblast growth factor(FGF) members, FGF19, FGF21, and FGF23, function as endocrine factors that regulate various metabolic processes. The unique feature of these endo- crine FGFs is the fact that they require Klotho proteins to bind to their cognate FGF recep- tors. Defects in Klotho or FGF23 result in disturbed mineral metabolism and accelerated aging. The aging phenotypes can be alleviated by correcting phosphate imbalance, leading us to hypothesize that phosphate accelerates aging. In contrast, overexpression of FGF21 extends life span in mice. Thus, the FGF-Klotho endocrine axes have emerged as key regula- tors of the aging process and are regarded as potential therapeutic targets for the treatment of age-related disorders.