A potential link between phosphate and aging--lessons from Klotho-deficient mice.
Phosphate homeostasis is maintained primarily by a bone-kidney endocrine axis. When phosphate is in excess, fibroblast growth factor-23 (FGF23) is secreted from bone and acts on kidney to promote phosphate excretion into urine. FGF23 also reduces serum vitamin D levels to suppress phosphate absorption from intestine. Thus, FGF23 functions as a hormone that induces negative phosphate balance. One critical feature of FGF23 is that it requires Klotho, a single-pass transmembrane protein expressed in renal tubules, as an obligate co-receptor to bind and activate cognate FGF receptors. Importantly, defects in either FGF23 or Klotho not only cause phosphate retention but also a premature-aging syndrome in mice, which can be rescued by resolving hyperphosphatemia. In addition, changes in extracellular and intracellular phosphate concentration affect glucose metabolism, insulin sensitivity, and oxidative stress in vivo and in vitro, which potentially affect aging processes. These findings suggest an unexpected link between inorganic phosphate and aging in mammals.
Kuro-o
Makoto
M
Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9072, USA. Makoto.Kuro-o@UTSouthwestern.edu
D000375:Aging / Q000378:metabolism*; D019588:Aging, Premature / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D006706:Homeostasis; D054559:Hyperphosphatemia; D007668:Kidney / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D010710:Phosphates / Q000378:metabolism* / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D012307:Risk Factors; D014807:Vitamin D / Q000378:metabolism
C000717428:Fgf23 protein, mouse; D010710:Phosphates; D017468:Receptors, Fibroblast Growth Factor; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23