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- Title
Klotho: An antiaging protein involved in mineral and vitamin D metabolism.
- Authors
Torres, P.-Ureña; Prié, D.; Molina-Blétry, V.; Beck, L.; Silve, C.; Friedlander, G.
- Abstract
Klotho gene mutation leads to a syndrome strangely resembling chronic kidney disease patients undergoing dialysis with multiple accelerated age-related disorders, including hypoactivity, sterility, skin thinning, muscle atrophy, osteoporosis, vascular calcifications, soft-tissue calcifications, defective hearing, thymus atrophy, pulmonary emphysema, ataxia, and abnormalities of the pituitary gland, as well as hypoglycemia, hyperphosphatemia, and paradoxically high-plasma calcitriol levels. Conversely, mice overexpressing klotho show an extended existence and a slow aging process through a mechanism that may involve the induction of a state of insulin and oxidant stress resistance. Two molecules are produced by the klotho gene, a membrane bound form and a circulating form. However, their precise biological roles and molecular functions have been only partly deciphered. Klotho can act as a circulating factor or hormone, which binds to a not yet identified high-affinity receptor and inhibits the intracellular insulin/insulin-like growth factor-1 (IGF-1) signaling cascade; klotho can function as a novel β-glucuronidase, which deglycosylates steroid β-glucuronides and the calcium channel transient receptor potential vallinoid-5 (TRPV5); as a cofactor essential for the stimulation of fibroblast growth factor (FGF) receptor by FGF23. The two last functions have propelled klotho to the group of key factors regulating mineral and vitamin D metabolism, and have also stimulated the interest of the nephrology community. The purpose of this review is to provide a nephrology-oriented overview of klotho and its potential implications in normal and altered renal function states.Kidney International (2007) 71, 730–737. doi:10.1038/sj.ki.5002163; published online 28 February 2007
- Subjects
MINERAL metabolism; PARATHYROID hormone; CALCIUM; PHOSPHORUS; CALCIFICATION; RENAL osteodystrophy
- Publication
Kidney International, 2007, Vol 71, Issue 8, p730
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/sj.ki.5002163