Evidence map›Paper›PMID 27714549›Full record

ArticleBrain imaging and behavior2017

Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging.

Jennifer S Yokoyama, Gabe Marx, Jesse A Brown, Luke W Bonham, Dan Wang, Giovanni Coppola, William W Seeley, Howard J Rosen, Bruce L Miller, Joel H Kramer and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain imaging and behavior, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 3 pooled it
6.3field-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

44 citing papers in PubMed, 3 syntheses or guidelines pooled it, 67 citations in OpenAlex.

  1. Pooled it
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  3. Pooled it
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  8. Review
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  11. Impact ofProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Associations Between Klotho Levels,Schizophrenia bulletin open · 2025
    Article
  13. Article
  14. Amyloid-β positivity is less prevalent in cognitively unimpairedJournal of Alzheimer's disease : JAD · 2024
    Article
  15. Article
  16. Article
  17. Review
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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

11 authors at 2 institutions in 1 country.

Jennifer S YokoyamaDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. jennifer.yokoyama@ucsf.edu.
Gabe MarxDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
Jesse A BrownDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
Luke W BonhamDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
Dan WangDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
Giovanni CoppolaDepartment of Neurology and Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at University of California, Los Angeles, CA, 90095, USA.
William W SeeleyDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
Howard J RosenDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
Bruce L MillerDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
Joel H KramerDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
Dena B DubalDepartment of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA. dena.dubal@ucsf.edu.
University of California, San Francisco · USUniversity of California, Los Angeles · US

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI BRUCE L MILLER · 2002 to 2026
$67.2M
Mechanisms of Executive Decline in Normal AgingR01AG032289 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kaitlin B Casaletto, JOEL H KRAMER · 2009 to 2026
$8.3M
Biological Predictors Of Brain Aging Trajectories Diversity Supplement: African American Outreach And The Intersection Between Social Determinants Of Health And Biomarkers Of Degenerative DiseaseRF1AG032289 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRAMER, JOEL H · 2020 to 2021
$5.3M
Effects of chronic inflammation on brain structure and functionR01AG048234 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRAMER, JOEL H · 2015 to 2019
$3.2M
Klotho and Neurodegenerative DiseaseR01NS092918 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DUBAL, DENA BOU · 2016 to 2020
$1.7M
RNA signatures of frontotemporal dementia and ALS due to C9ORF72 expansionK01AG049152 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOKOYAMA, JENNIFER S · 2015 to 2019
$648k
Collagen VI: Novel Mechanisms and Functions in Alzheimer's DiseaseK08AG034531 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DUBAL, DENA BOU · 2009 to 2013
$540k
NIA NIH HHS K01 AG049152NIA NIH HHS K08 AG034531NIA NIH HHS P01 AG019724NIA NIH HHS R01 AG032289NIA NIH HHS R01 AG048234NIA NIH HHS RF1 AG032289NINDS NIH HHS R01 NS092918
6 · The paper itself

Abstract

Cognitive decline is a major biomedical challenge as the global population ages. Elevated levels of the longevity factor klotho suppress aging, enhance cognition, and promote synaptic plasticity and neural resilience against aging and Alzheimer's disease (AD)-related pathogenic proteins. Here, we examined the relationship between human genetic variants of KLOTHO and systemic klotho levels - and assessed neuroanatomic correlates of serum klotho in a cohort of healthy older adults. Serum klotho levels were increased with KL-VS heterozygosity, as anticipated. We report, for the first time, that serum klotho levels were paradoxically decreased with KL-VS homozygosity. Further, we found that higher serum klotho levels were associated with measures of greater intrinsic connectivity in key functional networks of the brain vulnerable to aging and AD such as the fronto-parietal and default mode networks. Our findings suggest that elevated klotho promotes a resilient brain, possibly through increased network connectivity of critical brain regions.

Indexed as

AgedAgingBiomarkersConnectomeFemaleGenetic MarkersGlucuronidaseHumansKlotho ProteinsMaleNerve NetPolymorphism, Single NucleotideReproducibility of ResultsSensitivity and SpecificityTemporal LobeTissue DistributionBiomarkersGenetic MarkersGlucuronidaseKlotho ProteinsAgingCognitionConnectivityFrontal cortexGenetic variationImagingKlothoLongevityResilience

Identifiers

PMID27714549
PMCPMC5382127
OpenAlexW2527905058

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.