Evidence map›Paper›PMID 30451844›Full record

ArticleNature communications2018

Age-related declines in α-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration.

A Sahu, H Mamiya, S N Shinde, A Cheikhi, L L Winter, N V Vo, D Stolz, V Roginskaya, W Y Tang, C St Croix and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

111 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Therapeutic Lithium Enhances Klotho Expression and Mitochondrial Size and Branching in Human Cardiac Fibroblasts Involving Nuclear Factor-kappa B Inhibition.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026
    Article
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  7. Research progress on blood therapy for anti-aging.Journal of advanced research · 2026
    Review
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  11. Article
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  13. Article
  14. Article
  15. Underexplored terrain: effects of high priority environmental toxicants on skeletal muscle.Journal of toxicology and environmental health. Part B, Critical reviews · 2026
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

51 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

16 authors at 6 institutions in 1 country.

A SahuDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, 15213, PA, USA.
H MamiyaDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, 15213, PA, USA.
S N ShindeDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, 15213, PA, USA.
A CheikhiDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, 15213, PA, USA.
L L WinterDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, 15213, PA, USA.
N V VoDepartment of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, 15213, PA, USA.
D StolzDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, 15261, PA, USA.
V RoginskayaDepartment of Pharmacology & Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, 15232, PA, USA.
W Y TangDepartment of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, 21218-2608, MD, USA.
C St CroixDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, 15261, PA, USA.
L H SandersDepartment of Neurology, Duke University School of Medicine, Durham, 27704, NC, USA.
M FrantiResearch Beyond Borders: Boehringer-Ingelheim Pharmaceuticals, Ridgefield, 06877, CT, USA.
B Van HoutenDepartment of Pharmacology & Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, 15232, PA, USA.
T A RandoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
A BarchowskyDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, 15261, PA, USA.
F AmbrosioDepartment of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, 15213, PA, USA. ambrosiof@upmc.edu.
University of Pittsburgh · USUPMC Hillman Cancer Center · USBoehringer Ingelheim (United States) · USDuke University · USJohns Hopkins University · USVeterans Health Administration · US

Funding

San Antonio OAIC - Research Education Component (REC)P30AG044271 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Adam Salmon · 2015 to 2026
$14.1M
Technology Development P2CHD086843 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSIO, FABRISIA · 2015 to 2024
$10.5M
Mechanisms of arsenic-induced muscle morbidity and reducedregenerative capacityR01ES023696 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSIO, FABRISIA, BARCHOWSKY, AARON · 2014 to 2018
$2.1M
The Anti-Aging Role of Klotho in Skeletal Muscle RegenerationR01AG052978 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSIO, FABRISIA · 2017 to 2020
$2.0M
Request for a Nikon A1 confocal microscopeS10OD019973 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATKINS, SIMON C · 2015 to 2015
$358k
The Anti-Aging Role of Klotho in Skeletal Muscle RegenerationR56AG052978 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSIO, FABRISIA, VAN HOUTEN, BENNETT · 2016 to 2016
$178k
Regulation of Muscle Fibrosis in Response to Injury and AgingI01BX002324 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI RANDO, THOMAS A. · 2014 to 2021
–
BLRD VA I01 BX002324NIA NIH HHS P30 AG044271NIA NIH HHS R01 AG052978NIA NIH HHS R56 AG052978NICHD NIH HHS P2C HD086843NIEHS NIH HHS R01 ES023696NIH HHS S10 OD019973
6 · The paper itself

Abstract

While young muscle is capable of restoring the original architecture of damaged myofibers, aged muscle displays a markedly reduced regeneration. We show that expression of the "anti-aging" protein, α-Klotho, is up-regulated within young injured muscle as a result of transient Klotho promoter demethylation. However, epigenetic control of the Klotho promoter is lost with aging. Genetic inhibition of α-Klotho in vivo disrupted muscle progenitor cell (MPC) lineage progression and impaired myofiber regeneration, revealing a critical role for α-Klotho in the regenerative cascade. Genetic silencing of Klotho in young MPCs drove mitochondrial DNA (mtDNA) damage and decreased cellular bioenergetics. Conversely, supplementation with α-Klotho restored mtDNA integrity and bioenergetics of aged MPCs to youthful levels in vitro and enhanced functional regeneration of aged muscle in vivo in a temporally-dependent manner. These studies identify a role for α-Klotho in the regulation of MPC mitochondrial function and implicate α-Klotho declines as a driver of impaired muscle regeneration with age.

Indexed as

AgingAnimalsDNA MethylationDNA, MitochondrialEpigenesis, GeneticGene Expression Regulation, DevelopmentalGlucuronidaseKlotho ProteinsMiceMice, Inbred C57BLMice, KnockoutMitochondriaMuscle, SkeletalMyoblastsPromoter Regions, GeneticReceptors, Cell SurfaceDNA, MitochondrialGlucuronidaseKlotho ProteinsReceptors, Cell SurfaceRNA, Small Interfering

Identifiers

PMID30451844
PMCPMC6242898
OpenAlexW2901183439

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.