Evidence map›Paper›PMID 36351875›Full record

ArticleJournal of cachexia, sarcopenia and muscle2023

The impact of senescence on muscle wasting in chronic kidney disease.

Ying Huang, Bin Wang, Faten Hassounah, S Russ Price, Janet Klein, Tamer M A Mohamed, Yanhua Wang, Jeanie Park, Hui Cai, Xuemei Zhang and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

38 citing papers in PubMed, 59 citations in OpenAlex.

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  19. The gut microbiome, chronic kidney disease, and sarcopenia.Cell communication and signaling : CCS · 2024
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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 4 institutions in 2 countries.

Ying HuangRenal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA.
Bin WangRenal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA.
Faten HassounahRenal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA.
S Russ PriceDepartment of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.
Janet KleinRenal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA.
Tamer M A MohamedInstitute of Molecular Cardiology, University of Louisville, Louisville, Kentucky, USA.
Yanhua WangRenal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA.
Jeanie ParkRenal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA.
Hui CaiRenal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA.
Xuemei ZhangRenal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA.
Xiaonan H WangRenal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA.ORCID 0000-0002-1023-8499
Emory University · USCentral South University · CNEast Carolina University · USUniversity of Louisville · US

Funding

Neurovascular Regulation During Exercise In Humans With Chronic Kidney DiseaseR01HL135183 · NHLBI · EMORY UNIVERSITY · PI Jeanie Park · 2017 to 2026
$5.4M
Induction of Cardiomyocyte Proliferation via Transient Expression of Cell Cycle Factors as a Promising Therapy for Heart FailureR01HL147921 · NHLBI · UNIVERSITY OF LOUISVILLE · PI Tamer M A Mohamed, Jonathan Satin · 2020 to 2026
$5.3M
MicroRNA and Muscle Wasting in UremiaR01AR060268 · NIAMS · EMORY UNIVERSITY · PI WANG, XIAONAN H · 2012 to 2016
$1.7M
Sympatho-inhibition with Mindfulness in Chronic Kidney DiseaseR61AT010457 · NCCIH · EMORY UNIVERSITY · PI PARK, JEANIE · 2019 to 2020
$946k
Deciphering the Relationship Between Cardiomyocyte Metabolic Configuration and Cell Cycle Re-entryF32HL149140 · NHLBI · UNIVERSITY OF LOUISVILLE · PI ABOULEISA, RIHAM RAAFAT ELGHARIB · 2020 to 2023
$243k
BLRD VA I01 BX000994CSRD VA I01 CX001065NCCIH NIH HHS R61 AT010457NHLBI NIH HHS F32 HL149140NHLBI NIH HHS R01 HL135183NHLBI NIH HHS R01 HL147921NIAMS NIH HHS R01 AR060268
6 · The paper itself

Abstract

backgroundMuscle wasting is a common complication of chronic kidney disease (CKD) that is associated with higher mortality. Although the mechanisms of myofibre loss in CKD has been widely studied, the contribution of muscle precursor cell (MPC) senescence remains poorly understood. Senescent MPCs no longer proliferate and can produce proinflammatory factors or cytokines. In this study, we tested the hypothesis that the senescence associated secretory phenotype (SASP) of MPCs contributes to CKD-induced muscle atrophy and weakness.

methodsCKD was induced in mice by 5/6th nephrectomy. Kidney function, muscle size, and function were measured, and markers of atrophy, inflammation, and senescence were evaluated using immunohistochemistry, immunoblots, or qPCR. To study the impact of senescence, a senolytics cocktail of dasatinib + quercetin (D&Q) was given orally to mice for 8 weeks. To investigate CKD-induced senescence at the cellular level, primary MPCs were incubated with serum from CKD or control subjects. The roles of specific proteins in MPC senescence were studied using adenoviral transduction, siRNA, and plasmid transfection.

resultsIn the hindlimb muscles of CKD mice, (i) the senescence biomarker SA-β-gal was sharply increased (~30-fold); (ii) the DNA damage response marker γ-H2AX was increased 1.9-fold; and (iii) the senescence pathway markers p21 and p16

conclusionsSenescent MPCs are likely to contribute to the development of muscle wasting during CKD by producing inflammatory cytokines. Limiting senescence with senolytics ameliorated muscle wasting and improved muscle strength in vivo and restored cultured MPC functions. These results suggest potential new therapeutic targets to improve muscle health and function in CKD.

Indexed as

Cyclin-Dependent Kinase Inhibitor p16Renal Insufficiency, ChronicAnimalsCytokinesMiceMusclesMuscular AtrophyRNA, Small InterferingSenotherapeuticsCyclin-Dependent Kinase Inhibitor p16CytokinesRNA, Small InterferingSenotherapeuticsCachexiaCDK (cyclin-dependent kinase)CKDDNA damageMuscle precursor cellsSenescence

Identifiers

PMID36351875
PMCPMC9891952
OpenAlexW4308647100

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.