Evidence map›Paper›PMID 37400721›Full record

ArticleNature aging2023

Longevity factor klotho enhances cognition in aged nonhuman primates.

Stacy A Castner, Shweta Gupta, Dan Wang, Arturo J Moreno, Cana Park, Chen Chen, Yan Poon, Aaron Groen, Kenneth Greenberg, Nathaniel David and 4 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07216781 (Evaluating the Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans), which is not on this map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
31.0field-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.

NCT07216781 phase1active not recruitingnot on this mapstarted 2025, after this paper: background citation

Evaluating the Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans: An Interventional, Non-Placebo-Controlled Pilot Phase Study

TypeinterventionalSponsorMinicircleRan2025 to 2026Enrolled14ConditionsHealthy AdultsArmsInjectable Plasmid Klotho Gene Therapy
3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 99 citations in OpenAlex.

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  12. Research progress on blood therapy for anti-aging.Journal of advanced research · 2026
    Review
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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Stacy A CastnerDepartment of Psychiatry and VA Connecticut Healthcare System, Yale School of Medicine, West Haven, CT, USA.
Shweta GuptaDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Dan WangDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Arturo J MorenoDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Cana ParkDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Chen ChenDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Yan PoonUnity Biotechnology, Brisbane, CA, USA.
Aaron GroenUnity Biotechnology, Brisbane, CA, USA.ORCID http://orcid.org/0009-0003-0314-9230
Kenneth GreenbergUnity Biotechnology, Brisbane, CA, USA.
Nathaniel DavidUnity Biotechnology, Brisbane, CA, USA.
Tom BooneTom Boone Consulting, Newbury Park, CA, USA.
Mark G BaxterSection on Comparative Medicine, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.ORCID http://orcid.org/0000-0002-8907-0923
Graham V WilliamsDepartment of Psychiatry and VA Connecticut Healthcare System, Yale School of Medicine, West Haven, CT, USA.
Dena B DubalDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. Dena.Dubal@ucsf.edu.ORCID http://orcid.org/0000-0001-7504-4372
University of California, San Francisco · USUnity Biotechnology (United States) · USVA Connecticut Healthcare System · USWake Forest University · US

Funding

UT Southwestern O'Brien Kidney Research Core CenterP30DK079328 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI MOE, ORSON W · 2007 to 2021
$16.9M
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 K08 AG034531NIDDK NIH HHS P30 DK079328
6 · The paper itself

Abstract

Cognitive dysfunction in aging is a major biomedical challenge. Whether treatment with klotho, a longevity factor, could enhance cognition in human-relevant models such as in nonhuman primates is unknown and represents a major knowledge gap in the path to therapeutics. We validated the rhesus form of the klotho protein in mice showing it increased synaptic plasticity and cognition. We then found that a single administration of low-dose, but not high-dose, klotho enhanced memory in aged nonhuman primates. Systemic low-dose klotho treatment may prove therapeutic in aging humans.

Indexed as

GlucuronidaseLongevityAgedAgingAnimalsCognitionHumansMicePrimatesGlucuronidase

Identifiers

PMID37400721
PMCPMC10432271
OpenAlexW4382989585

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.