Evidence map›Paper›PMID 34365717›Full record

ArticleAging cell2021

Disrupted macrophage metabolic reprogramming in aged soleus muscle during early recovery following disuse atrophy.

Dennis K Fix, H Atakan Ekiz, Jonathan J Petrocelli, Alec M Mckenzie, Ziad S Mahmassani, Ryan M O'Connell, Micah J Drummond

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
1.3field-weighted citation impact, top 20% 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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.

  1. Pooled it
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  10. Macrophage immunometabolism: emerging targets for regrowth in aging muscle.American journal of physiology. Endocrinology and metabolism · 2025
    Review
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  15. Macrophage senescence in health and diseases.Acta pharmaceutica Sinica. B · 2024
    Review
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  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

7 authors at 1 institution in 1 country.

Dennis K FixMolecular Medicine Program, Department of Integrative Physiology and Nutrition, Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah, USA.
H Atakan EkizDepartment of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA.ORCID 0000-0001-7718-6841
Jonathan J PetrocelliMolecular Medicine Program, Department of Integrative Physiology and Nutrition, Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah, USA.
Alec M MckenzieMolecular Medicine Program, Department of Integrative Physiology and Nutrition, Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah, USA.
Ziad S MahmassaniMolecular Medicine Program, Department of Integrative Physiology and Nutrition, Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah, USA.
Ryan M O'ConnellDepartment of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA.
Micah J DrummondMolecular Medicine Program, Department of Integrative Physiology and Nutrition, Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah, USA.ORCID 0000-0001-5961-8890
University of Utah · US

Funding

LOOH-induced muscle atrophy with ageR01AG074535 · NIA · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Micah J Drummond, Katsuhiko Funai · 2022 to 2026
$3.0M
Cardiovasomobility Research Training ProgramT32HL139451 · NHLBI · UNIVERSITY OF UTAH · PI SUPIANO, MARK A, WRAY, D. WALTER · 2018 to 2022
$1.4M
Role of immune cells on the growth and recovery of aging muscleR21AG062923 · NIA · UNIVERSITY OF UTAH · PI DRUMMOND, MICAH J, O'CONNELL, RYAN M · 2019 to 2020
$477k
NHLBI NIH HHS T32 HL139451NIA NIH HHS R01 AG074535NIA NIH HHS R21 AG062923NIA NIH HHS R21AG062923
6 · The paper itself

Abstract

Aged skeletal muscle is characterized by poor muscle recovery following disuse coinciding with an impaired muscle pro-inflammatory macrophage response. Macrophage inflammatory status is regulated by its metabolic state, but little is understood of macrophage metabolism and its relation to macrophage inflammation in the context of muscle recovery and aging. Therefore, the purpose of this study was to thoroughly characterize macrophage metabolism and inflammation in aged muscle during early recovery following disuse atrophy using single cell transcriptomics and functional assays. Young (4-5 months) and old (20-22 months) male C57BL/6 mice underwent 14 days of hindlimb unloading followed by 4 days of ambulatory recovery. CD45+ cells were isolated from solei muscles and analyzed using 10x Genomics single cell RNA sequencing. We found that aged pro-inflammatory macrophage clusters were characterized with an impaired inflammatory and glycolytic transcriptome, and this dysregulation was accompanied by a suppression of HIF-1α and its immediate downstream target, Glut1. As a follow-up, bone marrow-derived macrophages were isolated from a separate cohort of young and old mice at 4-d recovery and were polarized to a pro-inflammatory phenotype and used for glycolysis stress test, phagocytosis activity assay, and targeted GC-MS metabolomics. Aged bone marrow-derived pro-inflammatory macrophages were characterized with impaired glycolysis and phagocytosis function, decreased succinate and an accumulation of glycolytic metabolic intermediates overall supporting reduced glycolytic flux and macrophage function. Our results indicate that the metabolic reprograming and function of aged skeletal muscle pro-inflammatory macrophages are dysfunctional during early recovery from disuse atrophy possibly attributing to attenuated regrowth.

Indexed as

AnimalsMacrophagesMaleMiceMice, Inbred C57BLMuscle, SkeletalMuscular Disorders, AtrophicglycolysisinflammationmetabolomicsscRNASeqsingle cell transcriptomics

Identifiers

PMID34365717
PMCPMC8441489
OpenAlexW3188000499

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.