Evidence map›Paper›PMID 34416035›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021

Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle.

Jonathan J Petrocelli, Ziad S Mahmassani, Dennis K Fix, Jessie A Montgomery, Paul T Reidy, Alec I McKenzie, Naomi M de Hart, Patrick J Ferrara, Joshua J Kelley, Hiroaki Eshima and 2 more

Open access · greenAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. 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
2.2field-weighted citation impact, top 11% 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, 35 citations in OpenAlex.

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  8. Metabolic regulation in the senescence process of stem cells.Stem cells translational medicine · 2025
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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

12 authors at 2 institutions in 1 country.

Jonathan J PetrocelliDepartment of Physical Therapy & Athletic Training, University of Utah, Salt Lake City, Utah, USA.
Ziad S MahmassaniDepartment of Physical Therapy & Athletic Training, University of Utah, Salt Lake City, Utah, USA.
Dennis K FixDepartment of Physical Therapy & Athletic Training, University of Utah, Salt Lake City, Utah, USA.
Jessie A MontgomeryDepartment of Chemistry, University of Utah, Salt Lake City, Utah, USA.
Paul T ReidyDepartment of Kinesiology, Nutrition and Health, Miami University, Oxford, Ohio, USA.
Alec I McKenzieDepartment of Internal Medicine, University of Utah, Salt Lake City, Utah, USA.
Naomi M de HartDepartment of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, USA.
Patrick J FerraraMolecular Medicine Program, University of Utah, Salt Lake City, Utah, USA.
Joshua J KelleyDepartment of Physical Therapy & Athletic Training, University of Utah, Salt Lake City, Utah, USA.
Hiroaki EshimaDepartment of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, USA.
Katsuhiko FunaiDepartment of Physical Therapy & Athletic Training, University of Utah, Salt Lake City, Utah, USA.
Micah J DrummondDepartment of Physical Therapy & Athletic Training, University of Utah, Salt Lake City, Utah, USA.ORCID https://orcid.org/0000-0001-5961-8890
University of Utah · USMiami University · US

Funding

PE methylation in skeletal muscle energy efficiencyR01DK107397 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI FUNAI, KATSUHIKO · 2017 to 2025
$3.8M
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
PE In Modulation of Energy Flux Through OxphosR01GM144613 · NIGMS · UNIVERSITY OF UTAH · PI FUNAI, KATSUHIKO · 2021 to 2024
$1.6M
Cardiovasomobility Research Training ProgramT32HL139451 · NHLBI · UNIVERSITY OF UTAH · PI SUPIANO, MARK A, WRAY, D. WALTER · 2018 to 2022
$1.4M
Mitochondrial phospholipids, ROS, and disuse atrophyR21AG063077 · NIA · UNIVERSITY OF UTAH · PI FUNAI, KATSUHIKO · 2019 to 2020
$419k
Amplifying muscle and metabolic recovery in aging using metformin and leucineR03AG064216 · NIA · UNIVERSITY OF UTAH · PI DRUMMOND, MICAH J · 2019 to 2020
$153k
NHLBI NIH HHS T32 HL139451NIA NIH HHS R01 AG074535NIA NIH HHS R03 AG064216NIA NIH HHS R21 AG063077NIDDK NIH HHS R01 DK107397NIGMS NIH HHS R01 GM144613
6 · The paper itself

Abstract

Loss of muscle mass and strength after disuse followed by impaired muscle recovery commonly occurs with aging. Metformin (MET) and leucine (LEU) individually have shown positive effects in skeletal muscle during atrophy conditions but have not been evaluated in combination nor tested as a remedy to enhance muscle recovery following disuse atrophy in aging. The purpose of this study was to determine if a dual treatment of metformin and leucine (MET + LEU) would prevent disuse-induced atrophy and/or promote muscle recovery in aged mice and if these muscle responses correspond to changes in satellite cells and collagen remodeling. Aged mice (22-24 months) underwent 14 days of hindlimb unloading (HU) followed by 7 or 14 days of reloading (7 or 14 days RL). MET, LEU, or MET + LEU was administered via drinking water and were compared to Vehicle (standard drinking water) and ambulatory baseline. We observed that during HU, MET + LEU resolved whole body grip strength and soleus muscle specific force decrements caused by HU. Gastrocnemius satellite cell abundance was increased with MET + LEU treatment but did not alter muscle size during disuse or recovery conditions. Moreover, MET + LEU treatment alleviated gastrocnemius collagen accumulation caused by HU and increased collagen turnover during 7 and 14 days RL driven by a decrease in collagen IV content. Transcriptional pathway analysis revealed that MET + LEU altered muscle hallmark pathways related to inflammation and myogenesis during HU. Together, the dual treatment of MET and LEU was able to increase muscle function, satellite cell content, and reduce collagen accumulation, thus improving muscle quality during disuse and recovery in aging.

Indexed as

AgingAMP-Activated Protein KinasesAnimalsBody WeightCollagenFibrosisHindlimb SuspensionImmunoglobulin GLeucineMaleMechanistic Target of Rapamycin Complex 1MetforminMiceMice, Inbred C57BLMuscle DevelopmentMuscle Fibers, SkeletalAMP-Activated Protein KinasesCollagenImmunoglobulin GLeucineMechanistic Target of Rapamycin Complex 1MetforminPrkaa1 protein, mouseagingextracellular matrixfibrosishindlimb unloadinginflammationreloading

Identifiers

PMID34416035
PMCPMC8384128
OpenAlexW3194008059

What OpenQuestion holds

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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.