Evidence map›Paper›PMID 40924478›Full record

ArticleJCI insight2025

Macrophage metabolic rewiring rejuvenates muscle Raman signatures and cellular remodeling during regrowth in aged mice.

Zachary J Fennel, Negar Kosari, Paul-Emile Bourrant, Elena M Yee, Robert J Castro, Anu S Kurian, Jonathan Palmer, Morgan Christensen, Katsuhiko Funai, Ryan M O'Connell and 2 more

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
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  4. Review
  5. Article
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

12 authors.

Zachary J FennelUtah Center for Metabolic Health.
Negar KosariDepartment of Biological Engineering, Utah State University, Logan Utah, USA.
Paul-Emile BourrantUtah Center for Metabolic Health.
Elena M YeeUtah Center for Metabolic Health.
Robert J CastroUtah Center for Metabolic Health.
Anu S KurianUtah Center for Metabolic Health.
Jonathan PalmerSpencer Fox Eccles School of Medicine, and.
Morgan ChristensenDepartment of Biological Engineering, Utah State University, Logan Utah, USA.
Katsuhiko FunaiUtah Center for Metabolic Health.
Ryan M O'ConnellDepartment of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah, USA.
Anhong ZhouDepartment of Biological Engineering, Utah State University, Logan Utah, USA.
Micah J DrummondUtah Center for Metabolic Health.

Funding

Interdisciplinary Training Program in MetabolismT32DK091317 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI SCOTT A SUMMERS · 2011 to 2026
$4.8M
Regulation of macrophage metabolism in aged muscle during recoveryR01AG076075 · NIA · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Micah J Drummond, Ryan M O'Connell · 2022 to 2026
$3.3M
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
Leveraging senotherapeutic properties of metformin to improve collagen remodeling during muscle regrowth in older adultsR01AG086328 · NIA · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Micah J Drummond · 2024 to 2026
$1.9M
NIA NIH HHS R01 AG074535NIA NIH HHS R01 AG076075NIA NIH HHS R01 AG086328NIDDK NIH HHS T32 DK091317
6 · The paper itself

Abstract

Impaired muscle regrowth in aging is underpinned by reduced proinflammatory macrophage function and subsequently impaired muscle cellular remodeling. Macrophage phenotype is metabolically controlled through TCA intermediate accumulation and activation of HIF1A. We hypothesized that transient hypoxia following disuse in old mice would enhance macrophage metabolic inflammatory function, thereby improving muscle cellular remodeling and recovery. Old (20 months) and young adult mice (4 months) were exposed to acute (24 hour) normobaric hypoxia immediately following 14 days of hind limb unloading and assessed during early reambulation (4 and 7 days) compared to age-matched controls. Treated aged mice had improved proinflammatory macrophage profiles, muscle cellular remodeling, and functional muscle recovery to the levels of young control mice. Likewise, young adult mice had enhanced muscle remodeling and functional recovery when treated with acute hypoxia. Treatment in aged mice restored the muscle molecular fingerprint and biochemical spectral patterns (Raman spectroscopy) observed in young mice and strongly correlated with improved collagen remodeling. Finally, intramuscular delivery of hypoxia-treated macrophages recapitulated the muscle remodeling and recovery effects of whole-body hypoxic exposure in old mice. These results emphasize the role of proinflammatory macrophages during muscle regrowth in aging and highlight immunometabolic approaches as a route to improve muscle cellular dynamics and regrowth.

Indexed as

AgingMacrophagesMuscle, SkeletalAnimalsHypoxiaMaleMiceMice, Inbred C57BLSpectrum Analysis, RamanAgingFibrosisImmunotherapyMacrophagesMetabolismMuscle biology

Identifiers

PMID40924478
PMCPMC12581675

What Socratic holds

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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 Socratic graph.