Evidence map›Paper›PMID 34196129›Full record

SynthesisJournal of cachexia, sarcopenia and muscle2021

Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle.

Sarah Voisin, Macsue Jacques, Shanie Landen, Nicholas R Harvey, Larisa M Haupt, Lyn R Griffiths, Sofiya Gancheva, Meriem Ouni, Markus Jähnert, Kevin J Ashton and 18 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Journal of cachexia, sarcopenia and muscle, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 7 pooled it
6.0field-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

54 citing papers in PubMed, 7 syntheses or guidelines pooled it, 83 citations in OpenAlex.

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  20. Molecular Framework of the Onset and Progression of Skeletal Muscle Aging.International journal of molecular sciences · 2025
    Review
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

28 authors at 11 institutions in 7 countries.

Sarah VoisinInstitute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Vic., Australia.ORCID 0000-0002-4074-7083
Macsue JacquesInstitute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Vic., Australia.
Shanie LandenInstitute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Vic., Australia.
Nicholas R HarveyFaculty of Health Sciences & Medicine, Bond University, Gold Coast, Qld, Australia.
Larisa M HauptCentre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Qld, Australia.
Lyn R GriffithsCentre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Qld, Australia.
Sofiya GanchevaGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Meriem OuniGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Markus JähnertGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Kevin J AshtonFaculty of Health Sciences & Medicine, Bond University, Gold Coast, Qld, Australia.
Vernon G CoffeyFaculty of Health Sciences & Medicine, Bond University, Gold Coast, Qld, Australia.
Jamie-Lee M ThompsonFaculty of Health Sciences & Medicine, Bond University, Gold Coast, Qld, Australia.
Thomas M DoeringSchool of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton, Qld, Australia.
Anne GaboryUniversité Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France.
Claudine JunienUniversité Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, France.
Robert CaiazzoUniv Lille, Inserm, CHU Lille, Pasteur Institute Lille, U1190 Translational Research for Diabetes, European Genomic Institute of Diabetes, Lille, France.
Hélène VerkindtUniv Lille, Inserm, CHU Lille, Pasteur Institute Lille, U1190 Translational Research for Diabetes, European Genomic Institute of Diabetes, Lille, France.
Violetta RaverdyUniv Lille, Inserm, CHU Lille, Pasteur Institute Lille, U1190 Translational Research for Diabetes, European Genomic Institute of Diabetes, Lille, France.
François PattouUniv Lille, Inserm, CHU Lille, Pasteur Institute Lille, U1190 Translational Research for Diabetes, European Genomic Institute of Diabetes, Lille, France.
Philippe FroguelUniv Lille, Inserm, CHU Lille, Pasteur Institute Lille, U1190 Translational Research for Diabetes, European Genomic Institute of Diabetes, Lille, France.
Jeffrey M CraigIMPACT Institute, Deakin University, Geelong Waurn Ponds Campus, Geelong, Vic., Australia.
Sara BlocquiauxPhysical Activity, Sport & Health Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium.
Martine ThomisPhysical Activity, Sport & Health Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium.
Adam P SharplesInstitute for Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway.
Annette SchürmannGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Michael RodenGerman Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Steve HorvathDepartment of Human Genetics and Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Nir EynonInstitute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Vic., Australia.
Deutsches Diabetes-Zentrum e.V. · DEInserm · FRBond University · AUVictoria University · AUÉcole Nationale Vétérinaire d'Alfort · FRKU Leuven · BEQueensland University of Technology · AUCentral Queensland University · AUNorwegian School of Sport Sciences · NORoyal Children's Hospital · AUUniversity of California, Los Angeles · US

Funding

Validation and optimization of epigenetic clocksU01AG060908 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2018 to 2022
$3.4M
Medical Research Council MR/R010676/1NIA NIH HHS U01 AG060908
6 · The paper itself

Abstract

backgroundKnowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans.

methodsWe conducted a large-scale epigenome-wide association study meta-analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18-89 years old). We explored the genomic context of age-related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with known transcriptomic and proteomic age-related changes in skeletal muscle. Finally, we updated our recently developed muscle epigenetic clock (https://bioconductor.org/packages/release/bioc/html/MEAT.html).

resultsWe identified 6710 differentially methylated regions at a stringent false discovery rate <0.005, spanning 6367 unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNA methylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylation at enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were nonetheless strongly enriched for genes showing age-related differential mRNA and protein expression. After adding a substantial number of samples from five datasets (+371), the updated version of the muscle clock (MEAT 2.0, total n = 1053 samples) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years in age prediction error), suggesting that the original version of the muscle clock was very accurate.

conclusionsWe provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscle and reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation. We have made our results available as an open-access, user-friendly, web-based tool called MetaMeth (https://sarah-voisin.shinyapps.io/MetaMeth/).

Indexed as

DNA MethylationProteomicsAdolescentAdultAgedAged, 80 and overCpG IslandsEpigenesis, GeneticFemaleHumansMaleMiddle AgedMuscle, SkeletalYoung AdultAgeingDNA methylationEpigenetic clockEpigeneticsMeta-analysisOmicsSkeletal muscle

Identifiers

PMID34196129
PMCPMC8350206
OpenAlexW3174001059

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.