Evidence map›Paper›PMID 34374422›Full record

ReviewClinical science (London, England : 1979)2021

Klotho and calciprotein particles as therapeutic targets against accelerated ageing.

Makoto Kuro-O

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

Review in Clinical science (London, England : 1979), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

36 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Review
  6. Article
  7. Article
  8. NSAID use may decrease serum Klotho levels.Frontiers in endocrinology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review
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

1 author at 1 institution in 1 country.

Makoto Kuro-ODivision of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.ORCID 0000-0003-0018-7269
Jichi Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The klotho gene, named after a Greek goddess who spins the thread of life, was identified as a putative 'ageing-suppressor' gene. Klotho-deficient mice exhibit complex ageing-like phenotypes including hypogonadism, arteriosclerosis (vascular calcification), cardiac hypertrophy, osteopenia, sarcopenia, frailty, and premature death. Klotho protein functions as the obligate co-receptor for fibroblast growth factor-23 (FGF23), a bone-derived hormone that promotes urinary phosphate excretion in response to phosphate intake. Thus, Klotho-deficient mice suffer not only from accelerated ageing but also from phosphate retention due to impaired phosphate excretion. Importantly, restoration of the phosphate balance by placing Klotho-deficient mice on low phosphate diet rescued them from premature ageing, leading us to the notion that phosphate accelerates ageing. Because the extracellular fluid is super-saturated in terms of phosphate and calcium ions, an increase in the phosphate concentration can trigger precipitation of calcium-phosphate. In the blood, calcium-phosphate precipitated upon increase in the blood phosphate concentration is adsorbed by serum protein fetuin-A to form colloidal nanoparticles called calciprotein particles (CPPs). In the urine, CPPs appear in the renal tubular fluid when FGF23 increases phosphate load excreted per nephron. CPPs can induce cell damage, ectopic calcification, and inflammatory responses. CPPs in the blood can induce arteriosclerosis and non-infectious chronic inflammation, whereas CPPs in the urine can induce renal tubular damage and interstitial inflammation/fibrosis. Thus, we propose that CPPs behave like a pathogen that accelerates ageing and should be regarded as a novel therapeutic target against age-related disorders including chronic kidney disease.

Indexed as

NanoparticlesAge FactorsAgingalpha-2-HS-GlycoproteinAnimalsCalcium PhosphatesCardiovascular DiseasesFibroblast Growth Factor-23HumansKidneyKlotho ProteinsPhosphorusRenal EliminationRenal Insufficiency, Chronicalpha-2-HS-Glycoproteincalcium phosphateCalcium PhosphatesFibroblast Growth Factor-23Klotho ProteinsPhosphorusageingcalciprotein particleschronic kidney diseasefibroblast growth factorsKlothophosphate

Identifiers

PMID34374422
PMCPMC8355631
OpenAlexW3190226568

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.