Molecular basis of klotho

From gene to function in aging

Yuechi Xu, Zhongjie Sun

Research output: Contribution to journalReview article

91 Citations (Scopus)

Abstract

The discovery of the Klotho (KL) gene, which was originally identified as a putative aging-suppressor gene, has generated tremendous interest and has advanced understanding of the aging process. In mice, the overexpression of theKLgeneextends the life span, whereas mutations to theKLgeneshorten the life span. Thehuman KL gene encodes the β-Klotho protein, which is a multifunctional protein that regulates the metabolism of phosphate, calcium, and vitamin D.β-Klotho also may function as a hormone, although theβ-Klotho receptor(s) has not been found. Point mutations of the KL gene in humans are associated with hypertension and kidney disease, which suggests that β-Klotho may be essential to the maintenance of normal renal function. Three β-Klotho protein types with potentially different functions have been identified: a full-length transmembrane β-Klotho, a truncated soluble β-Klotho, and a secreted β-Klotho. Recent evidence suggests that β-Klotho suppresses the insulin andWntsignaling pathways, inhibits oxidative stress, and regulates phosphatase and calcium absorption. In this review, we provide an update on recent advances in the understanding of the molecular, genetic, biochemical, and physiological properties of the KL gene. Specifically, this review focuses on the structure of the KL gene and the factors that regulate KL gene transcription, the key sites in the regulation of β-Klotho enzyme activity, the β-Klotho signaling pathways, and the molecular mechanisms that underlie β-Klotho function. This current understanding of the molecular biology of the β-Klotho protein may offer new insights into its function and role in aging.

Original languageEnglish (US)
Pages (from-to)174-193
Number of pages20
JournalEndocrine Reviews
Volume36
Issue number2
DOIs
StatePublished - Jan 1 2015

Fingerprint

Genes
Molecular Biology
Suppressor Genes
Kidney Diseases
Genetic Association Studies
Phosphoric Monoester Hydrolases
Point Mutation
Vitamin D
Oxidative Stress
Maintenance
Hormones
Insulin
Hypertension
Calcium
Kidney
Mutation
Enzymes
klotho protein
Proteins
calcium phosphate

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Molecular basis of klotho : From gene to function in aging. / Xu, Yuechi; Sun, Zhongjie.

In: Endocrine Reviews, Vol. 36, No. 2, 01.01.2015, p. 174-193.

Research output: Contribution to journalReview article

@article{411f86e7fa944255977cad5d12f3fa95,
title = "Molecular basis of klotho: From gene to function in aging",
abstract = "The discovery of the Klotho (KL) gene, which was originally identified as a putative aging-suppressor gene, has generated tremendous interest and has advanced understanding of the aging process. In mice, the overexpression of theKLgeneextends the life span, whereas mutations to theKLgeneshorten the life span. Thehuman KL gene encodes the β-Klotho protein, which is a multifunctional protein that regulates the metabolism of phosphate, calcium, and vitamin D.β-Klotho also may function as a hormone, although theβ-Klotho receptor(s) has not been found. Point mutations of the KL gene in humans are associated with hypertension and kidney disease, which suggests that β-Klotho may be essential to the maintenance of normal renal function. Three β-Klotho protein types with potentially different functions have been identified: a full-length transmembrane β-Klotho, a truncated soluble β-Klotho, and a secreted β-Klotho. Recent evidence suggests that β-Klotho suppresses the insulin andWntsignaling pathways, inhibits oxidative stress, and regulates phosphatase and calcium absorption. In this review, we provide an update on recent advances in the understanding of the molecular, genetic, biochemical, and physiological properties of the KL gene. Specifically, this review focuses on the structure of the KL gene and the factors that regulate KL gene transcription, the key sites in the regulation of β-Klotho enzyme activity, the β-Klotho signaling pathways, and the molecular mechanisms that underlie β-Klotho function. This current understanding of the molecular biology of the β-Klotho protein may offer new insights into its function and role in aging.",
author = "Yuechi Xu and Zhongjie Sun",
year = "2015",
month = "1",
day = "1",
doi = "10.1210/er.2013-1079",
language = "English (US)",
volume = "36",
pages = "174--193",
journal = "Endocrine Reviews",
issn = "0163-769X",
publisher = "The Endocrine Society",
number = "2",

}

TY - JOUR

T1 - Molecular basis of klotho

T2 - From gene to function in aging

AU - Xu, Yuechi

AU - Sun, Zhongjie

PY - 2015/1/1

Y1 - 2015/1/1

N2 - The discovery of the Klotho (KL) gene, which was originally identified as a putative aging-suppressor gene, has generated tremendous interest and has advanced understanding of the aging process. In mice, the overexpression of theKLgeneextends the life span, whereas mutations to theKLgeneshorten the life span. Thehuman KL gene encodes the β-Klotho protein, which is a multifunctional protein that regulates the metabolism of phosphate, calcium, and vitamin D.β-Klotho also may function as a hormone, although theβ-Klotho receptor(s) has not been found. Point mutations of the KL gene in humans are associated with hypertension and kidney disease, which suggests that β-Klotho may be essential to the maintenance of normal renal function. Three β-Klotho protein types with potentially different functions have been identified: a full-length transmembrane β-Klotho, a truncated soluble β-Klotho, and a secreted β-Klotho. Recent evidence suggests that β-Klotho suppresses the insulin andWntsignaling pathways, inhibits oxidative stress, and regulates phosphatase and calcium absorption. In this review, we provide an update on recent advances in the understanding of the molecular, genetic, biochemical, and physiological properties of the KL gene. Specifically, this review focuses on the structure of the KL gene and the factors that regulate KL gene transcription, the key sites in the regulation of β-Klotho enzyme activity, the β-Klotho signaling pathways, and the molecular mechanisms that underlie β-Klotho function. This current understanding of the molecular biology of the β-Klotho protein may offer new insights into its function and role in aging.

AB - The discovery of the Klotho (KL) gene, which was originally identified as a putative aging-suppressor gene, has generated tremendous interest and has advanced understanding of the aging process. In mice, the overexpression of theKLgeneextends the life span, whereas mutations to theKLgeneshorten the life span. Thehuman KL gene encodes the β-Klotho protein, which is a multifunctional protein that regulates the metabolism of phosphate, calcium, and vitamin D.β-Klotho also may function as a hormone, although theβ-Klotho receptor(s) has not been found. Point mutations of the KL gene in humans are associated with hypertension and kidney disease, which suggests that β-Klotho may be essential to the maintenance of normal renal function. Three β-Klotho protein types with potentially different functions have been identified: a full-length transmembrane β-Klotho, a truncated soluble β-Klotho, and a secreted β-Klotho. Recent evidence suggests that β-Klotho suppresses the insulin andWntsignaling pathways, inhibits oxidative stress, and regulates phosphatase and calcium absorption. In this review, we provide an update on recent advances in the understanding of the molecular, genetic, biochemical, and physiological properties of the KL gene. Specifically, this review focuses on the structure of the KL gene and the factors that regulate KL gene transcription, the key sites in the regulation of β-Klotho enzyme activity, the β-Klotho signaling pathways, and the molecular mechanisms that underlie β-Klotho function. This current understanding of the molecular biology of the β-Klotho protein may offer new insights into its function and role in aging.

UR - http://www.scopus.com/inward/record.url?scp=84929391863&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929391863&partnerID=8YFLogxK

U2 - 10.1210/er.2013-1079

DO - 10.1210/er.2013-1079

M3 - Review article

VL - 36

SP - 174

EP - 193

JO - Endocrine Reviews

JF - Endocrine Reviews

SN - 0163-769X

IS - 2

ER -