Evidence map›Paper›PMID 25695404›Full record

ReviewEndocrine reviews2015

Molecular basis of Klotho: from gene to function in aging.

Yuechi Xu, Zhongjie Sun

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Endocrine reviews, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 318 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
318citing papers in PubMed, 4 pooled it
19.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

318 citing papers in PubMed, 4 syntheses or guidelines pooled it, 538 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. [Effect of pioglitazone on periodontitis-related renal injury in mice and its relationship with Klotho].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2026
    Article
  15. Article
  16. Article
  17. Chronic Kidney Disease and Cellular Senescence.International journal of molecular sciences · 2026
    Review
  18. Article
  19. Article
  20. Article

258 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Yuechi XuDepartment of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
Zhongjie Sun
University of Oklahoma Health Sciences Center · US

Funding

Investigation into Heart AgingR01AG049780 · NIA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI SUN, ZHONGJIE · 2016 to 2020
$2.4M
Regulation of Blood Pressure by KlothoR01HL102074 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SUN, ZHONGJIE · 2011 to 2014
$2.1M
Molecular Mechanism of Kidney AgingR01DK093403 · NIDDK · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SUN, ZHONGJIE · 2012 to 2016
$1.6M
Anti-aging gene klotho: a novel therapeutic target in calcific aortic valve diseaseR01HL118558 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI SUN, ZHONGJIE · 2014 to 2017
$1.5M
Molecular Mechanism of Arterial StiffeningR01HL105302 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SUN, ZHONGJIE · 2010 to 2014
$1.4M
NHLBI NIH HHS R01 HL102074NHLBI NIH HHS R01 HL105302NHLBI NIH HHS R01 HL118558NIA NIH HHS R01 AG049780NIDDK NIH HHS R01 DK093403
6 · The paper itself

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 the KL gene extends the life span, whereas mutations to the KL gene shorten the life span. The human KL gene encodes the α-Klotho protein, which is a multifunctional protein that regulates the metabolism of phosphate, calcium, and vitamin D. α-Klotho also may function as a hormone, although the α-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 α-Klotho may be essential to the maintenance of normal renal function. Three α-Klotho protein types with potentially different functions have been identified: a full-length transmembrane α-Klotho, a truncated soluble α-Klotho, and a secreted α-Klotho. Recent evidence suggests that α-Klotho suppresses the insulin and Wnt signaling 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 α-Klotho enzyme activity, the α-Klotho signaling pathways, and the molecular mechanisms that underlie α-Klotho function. This current understanding of the molecular biology of the α-Klotho protein may offer new insights into its function and role in aging.

Indexed as

AgingCalciumGlucuronidaseHumansKlotho ProteinsOxidative StressPhosphatesSignal TransductionVitamin DWnt Signaling PathwayCalciumGlucuronidaseKlotho ProteinsPhosphatesVitamin D

Identifiers

PMID25695404
PMCPMC4399270
OpenAlexW2169020430

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.