A potential link between phosphate and aging-Lessons from Klotho-deficient mice

Makoto Kuro-o

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)270-275
Number of pages6
JournalMechanisms of Ageing and Development
Volume131
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Phosphates
Kidney
Premature Aging
Hyperphosphatemia
Bone and Bones
Fibroblast Growth Factor Receptors
Vitamin D
Intestines
Insulin Resistance
Mammals
Oxidative Stress
Homeostasis
fibroblast growth factor 23
Urine
Hormones
Glucose
Serum
Proteins

Keywords

  • CKD
  • FGF23
  • Klotho
  • Phosphate
  • Vitamin D

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

Cite this

A potential link between phosphate and aging-Lessons from Klotho-deficient mice. / Kuro-o, Makoto.

In: Mechanisms of Ageing and Development, Vol. 131, No. 4, 04.2010, p. 270-275.

Research output: Contribution to journalArticle

@article{c94837036e4d4ba8b0182972c95eb03c,
title = "A potential link between phosphate and aging-Lessons from Klotho-deficient mice",
abstract = "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.",
keywords = "CKD, FGF23, Klotho, Phosphate, Vitamin D",
author = "Makoto Kuro-o",
year = "2010",
month = "4",
doi = "10.1016/j.mad.2010.02.008",
language = "English (US)",
volume = "131",
pages = "270--275",
journal = "Mechanisms of Ageing and Development",
issn = "0047-6374",
publisher = "Elsevier Ireland Ltd",
number = "4",

}

TY - JOUR

T1 - A potential link between phosphate and aging-Lessons from Klotho-deficient mice

AU - Kuro-o, Makoto

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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.

KW - CKD

KW - FGF23

KW - Klotho

KW - Phosphate

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=77952544259&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952544259&partnerID=8YFLogxK

U2 - 10.1016/j.mad.2010.02.008

DO - 10.1016/j.mad.2010.02.008

M3 - Article

C2 - 20197072

AN - SCOPUS:77952544259

VL - 131

SP - 270

EP - 275

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

SN - 0047-6374

IS - 4

ER -