Evidence map›Paper›PMID 41676692›Full record

ArticlebioRxiv : the preprint server for biology2026

COUNTERING AGE-ASSOCIATED ALTERATIONS IN OLIGODENDROCYTE-DERIVED EXTRACELLULAR MATRIX REJUVENATES COGNITION.

Amber R Philp, L Remesal, Karishma J B Pratt, Jason C Maynard, Shanan Sahota, Turan Aghayev, Gregor Bieri, Rebecca Chu, Gabriel Avillion, Juliana Sucharov-Costa and 10 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

20 authors.

Amber R PhilpDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.ORCID 0009-0003-7411-4836
L RemesalDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Karishma J B PrattDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Jason C MaynardDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
Shanan SahotaDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Turan AghayevDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Gregor BieriDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Rebecca ChuDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Gabriel AvillionDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Juliana Sucharov-CostaDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Yasuhiro FuseyaDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Rhea MisraDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Shir MandelboumDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Bende ZouAfaSci Research Laboratory, Redwood City, CA, USA.
Julien CouthouisDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Xinmin S XieAfaSci Research Laboratory, Redwood City, CA, USA.
Stephen P J FancyDepartment of Neurology and Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
Takakuni MakiDepartment of Neurology, Kyoto University, Graduate School of Medicine, Kyoto, Japan.
Saul A VilledaDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA.

Funding

Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher · 2020 to 2026
$4.5M
Systemic Mechanisms of Brain RejuvenationR01AG077816 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAUL A VILLEDA · 2022 to 2026
$2.7M
Role of O-GlcNAcylation in Regulating Neurodegeneration in Aging and Alzheimer’s DiseaseRF1AG062357 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VILLEDA, SAUL A · 2018 to 2018
$2.0M
Investigating the role of the exercise blood factor Gpld1 in restoring brain vasculature function and cognition in agingF32AG081038 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIERI, GREGOR · 2023 to 2024
$151k
The Role of Peripheral Aged CD8+ T Cells in Hippocampal-Dependent Cognitive DeclineF31AG086042 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Juliana Sucharov Costa · 2024 to 2026
$138k
NIA NIH HHS F31 AG086042NIA NIH HHS F32 AG081038NIA NIH HHS R01 AG077816NIA NIH HHS RF1 AG062357NIGMS NIH HHS T32 GM136547
6 · The paper itself

Abstract

Efforts to rejuvenate age-related cognitive decline have predominantly targeted neurons, often overlooking non-neuronal cell types in the aging brain. Here, we show that countering alterations in oligodendrocyte-derived extracellular matrix (ECM) in the aging hippocampus restores cognition. We identify broad age-associated transcriptional and proteomic changes in oligodendrocytes, including dysregulation of the matrisome, with marked upregulation of ECM components and associated regulators with age. Among these, we detect an increase in Hyaluronan and proteoglycan link protein 2 (HAPLN2), an oligodendrocyte-derived core matrisome protein that locates specifically at the nodes of Ranvier, in the hippocampus of aged mice and older humans. Hapln2 overexpression in oligodendrocytes of young mice recapitulated age-related memory impairments. Conversely, abrogating the age-related increase in Hapln2 induced synaptic plasticity-related hippocampal transcriptional signatures and improved memory in aged mice. Together, these data define oligodendrocyte-derived ECM remodeling as a hallmark of brain aging that can be targeted to rescue cognitive decline.

Identifiers

PMID41676692
PMCPMC12889591

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.