Evidence map›Paper›PMID 37670389›Full record

SynthesisBiology of sex differences2023

Sex differences in muscle protein expression and DNA methylation in response to exercise training.

Shanie Landen, Macsue Jacques, Danielle Hiam, Javier Alvarez-Romero, Ralf B Schittenhelm, Anup D Shah, Cheng Huang, Joel R Steele, Nicholas R Harvey, Larisa M Haupt and 5 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Biology of sex differences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
9.6field-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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Molecular Effects of Physical Activity and Body Composition: A Systematic Review and Meta-Analysis.International journal of environmental research and public health · 2025
    Pooled it
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  16. DNA Methylation in the Adaptive Response to Exercise.Sports medicine (Auckland, N.Z.) · 2024
    Review
  17. Article
  18. Article
  19. Article
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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

15 authors at 8 institutions in 2 countries.

Shanie LandenInstitute for Health and Sport (iHeS), Victoria University, Melbourne, Australia.
Macsue JacquesInstitute for Health and Sport (iHeS), Victoria University, Melbourne, Australia.
Danielle HiamInstitute for Health and Sport (iHeS), Victoria University, Melbourne, Australia.
Javier Alvarez-RomeroInstitute for Health and Sport (iHeS), Victoria University, Melbourne, Australia.
Ralf B SchittenhelmMonash Proteomics and Metabolomics Facility, Monash University, Melbourne, Australia.
Anup D ShahMonash Proteomics and Metabolomics Facility, Monash University, Melbourne, Australia.
Cheng HuangMonash Proteomics and Metabolomics Facility, Monash University, Melbourne, Australia.
Joel R SteeleMonash Proteomics and Metabolomics Facility, Monash University, Melbourne, Australia.
Nicholas R HarveyFaculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, 4226, Australia.
Larisa M HauptCentre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD, 4059, Australia.
Lyn R GriffithsCentre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD, 4059, Australia.
Kevin J AshtonFaculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, 4226, Australia.
Séverine LamonInstitute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia.
Sarah VoisinInstitute for Health and Sport (iHeS), Victoria University, Melbourne, Australia.
Nir EynonInstitute for Health and Sport (iHeS), Victoria University, Melbourne, Australia. Nir.Eynon@monash.edu.ORCID http://orcid.org/0000-0003-4046-8276
Monash University · AUBond University · AUDeakin University · AUQueensland University of Technology · AUVictoria University · AUAustralian Regenerative Medicine Institute · AUHudson Institute of Medical Research · AUUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundExercise training elicits changes in muscle physiology, epigenomics, transcriptomics, and proteomics, with males and females exhibiting differing physiological responses to exercise training. However, the molecular mechanisms contributing to the differing adaptations between the sexes are poorly understood.

methodsWe performed a meta-analysis for sex differences in skeletal muscle DNA methylation following an endurance training intervention (Gene SMART cohort and E-MTAB-11282 cohort). We investigated for sex differences in the skeletal muscle proteome following an endurance training intervention (Gene SMART cohort). Lastly, we investigated whether the methylome and proteome are associated with baseline cardiorespiratory fitness (maximal oxygen consumption; VO

resultsHere, we investigated for the first time, DNA methylome and proteome sex differences in response to exercise training in human skeletal muscle (n = 78; 50 males, 28 females). We identified 92 DNA methylation sites (CpGs) associated with exercise training; however, no CpGs changed in a sex-dependent manner. In contrast, we identified 189 proteins that are differentially expressed between the sexes following training, with 82 proteins differentially expressed between the sexes at baseline. Proteins showing the most robust sex-specific response to exercise include SIRT3, MRPL41, and MBP. Irrespective of sex, cardiorespiratory fitness was associated with robust methylome changes (19,257 CpGs) and no proteomic changes. We did not observe sex differences in the association between cardiorespiratory fitness and the DNA methylome. Integrative multi-omic analysis identified sex-specific mitochondrial metabolism pathways associated with exercise responses. Lastly, exercise training and cardiorespiratory fitness shifted the DNA methylomes to be more similar between the sexes.

conclusionsWe identified sex differences in protein expression changes, but not DNA methylation changes, following an endurance exercise training intervention; whereas we identified no sex differences in the DNA methylome or proteome response to lifelong training. Given the delicate interaction between sex and training as well as the limitations of the current study, more studies are required to elucidate whether there is a sex-specific training effect on the DNA methylome. We found that genes involved in mitochondrial metabolism pathways are differentially modulated between the sexes following endurance exercise training. These results shed light on sex differences in molecular adaptations to exercise training in skeletal muscle.

Indexed as

Muscle ProteinsProteomeDNA MethylationExerciseFemaleHumansMaleMuscle, SkeletalMuscle ProteinsProteomeDNA methylationEpigeneticsExerciseProteomeSex differencesSkeletal muscle

Identifiers

PMID37670389
PMCPMC10478435
OpenAlexW4386443039

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.