Evidence map›Paper›PMID 37749958›Full record

ArticleAging cell2023

Senolytic treatment reduces oxidative protein stress in an aging male murine model of post-traumatic osteoarthritis.

Alexander F Chin, Jin Han, Cristina C Clement, Younghwan Choi, Hong Zhang, Maria Browne, Ok Hee Jeon, Jennifer H Elisseeff

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

Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
9.4field-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.

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

29 citing papers in PubMed, 38 citations in OpenAlex.

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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

8 authors at 3 institutions in 3 countries.

Alexander F ChinTranslational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0003-0498-2577
Jin HanTranslational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0001-8799-5140
Cristina C ClementDepartment of Radiation Oncology, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, New York, USA.
Younghwan ChoiTranslational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hong ZhangTranslational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Maria BrowneTranslational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ok Hee JeonTranslational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jennifer H ElisseeffTranslational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-5066-1996
Johns Hopkins University · USBloomberg (United States) · USCornell University · US

Funding

Translational Aging Research Training ProgramT32AG058527 · NIA · JOHNS HOPKINS UNIVERSITY · PI Peter M. Abadir, Esther Seunghee Oh · 2018 to 2026
$4.0M
NIA NIH HHS T32 AG058527
6 · The paper itself

Abstract

Senolytic drugs are designed to selectively clear senescent cells (SnCs) that accumulate with injury or aging. In a mouse model of osteoarthritis (OA), senolysis yields a pro-regenerative response, but the therapeutic benefit is reduced in aged mice. Increased oxidative stress is a hallmark of advanced age. Therefore, here we investigate whether senolytic treatment differentially affects joint oxidative load in young and aged animals. We find that senolysis by a p53/MDM2 interaction inhibitor, UBX0101, reduces protein oxidative modification in the aged arthritic knee joint. Mass spectrometry coupled with protein interaction network analysis and biophysical stability prediction of extracted joint proteins revealed divergent responses to senolysis between young and aged animals, broadly suggesting that knee regeneration and cellular stress programs are contrarily poised to respond as a function of age. These opposing responses include differing signatures of protein-by-protein oxidative modification and abundance change, disparate quantitative trends in modified protein network centrality, and contrasting patterns of oxidation-induced folding free energy perturbation between young and old. We develop a composite sensitivity score to identify specific key proteins in the proteomes of aged osteoarthritic joints, thereby nominating prospective therapeutic targets to complement senolytics.

Indexed as

OsteoarthritisSenotherapeuticsAgingAnimalsCellular SenescenceDisease Models, AnimalMaleMiceOxidative StressSenotherapeuticsagingcellular senescencemouseosteoarthritisoxidative stressprotein chemistryproteomicsreactive oxygen

Identifiers

PMID37749958
PMCPMC10652304
OpenAlexW4387033531

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.