Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Molecular landscape of sex- and modality-specific exercise adaptation in human skeletal muscle through large-scale multi-omics integration

Jacques, Macsue ; Landen, Shanie ; Sharples, Adam P. ; Garnham, Andrew ; Schittenhelm, Ralf ; Steele, Joel ; Heikkinen, Aino ; Sillanpää, Elina ; Ollikainen, Miina and Broatch, James , et al. (2025) In Cell Reports 44(6).
Abstract

We investigated the molecular mechanisms of exercise adaptations in human muscle by integrating genome, methylome, transcriptome, and proteome data from over 1,000 participants (2,340 muscle samples). We identified distinctive signatures associated with maximal oxygen consumption (VO2max), and multi-omics integration uncovered five key genes as robust exercise markers across layers, with transcription factors functioning as activators, synergizing with DNA methylation to regulate gene expression. Minimal sex differences were observed, while modality-specific analysis highlighted distinct pathways for aerobic and resistance exercise, contrasting with muscle disuse patterns. Finally, we created a webtool, OMAx, featuring our... (More)

We investigated the molecular mechanisms of exercise adaptations in human muscle by integrating genome, methylome, transcriptome, and proteome data from over 1,000 participants (2,340 muscle samples). We identified distinctive signatures associated with maximal oxygen consumption (VO2max), and multi-omics integration uncovered five key genes as robust exercise markers across layers, with transcription factors functioning as activators, synergizing with DNA methylation to regulate gene expression. Minimal sex differences were observed, while modality-specific analysis highlighted distinct pathways for aerobic and resistance exercise, contrasting with muscle disuse patterns. Finally, we created a webtool, OMAx, featuring our individual omics and integration analysis. These findings provide a comprehensive multi-omics framework for understanding exercise-induced molecular adaptations, offering insights into muscle health, cardiorespiratory fitness, and their roles in aging and disease prevention.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CP: Metabolism, DNA methylation, epigenetics, exercise, gene expression, Multi Omics, proteomic, skeletal muscle, transcriptomic, VO
in
Cell Reports
volume
44
issue
6
article number
115750
publisher
Cell Press
external identifiers
  • pmid:40445834
  • scopus:105006740608
ISSN
2639-1856
DOI
10.1016/j.celrep.2025.115750
language
English
LU publication?
yes
id
1bba8bea-e8d6-46d3-8338-eba4eae7d971
date added to LUP
2025-08-01 09:33:28
date last changed
2025-08-01 09:33:47
@article{1bba8bea-e8d6-46d3-8338-eba4eae7d971,
  abstract     = {{<p>We investigated the molecular mechanisms of exercise adaptations in human muscle by integrating genome, methylome, transcriptome, and proteome data from over 1,000 participants (2,340 muscle samples). We identified distinctive signatures associated with maximal oxygen consumption (VO<sub>2max</sub>), and multi-omics integration uncovered five key genes as robust exercise markers across layers, with transcription factors functioning as activators, synergizing with DNA methylation to regulate gene expression. Minimal sex differences were observed, while modality-specific analysis highlighted distinct pathways for aerobic and resistance exercise, contrasting with muscle disuse patterns. Finally, we created a webtool, OMAx, featuring our individual omics and integration analysis. These findings provide a comprehensive multi-omics framework for understanding exercise-induced molecular adaptations, offering insights into muscle health, cardiorespiratory fitness, and their roles in aging and disease prevention.</p>}},
  author       = {{Jacques, Macsue and Landen, Shanie and Sharples, Adam P. and Garnham, Andrew and Schittenhelm, Ralf and Steele, Joel and Heikkinen, Aino and Sillanpää, Elina and Ollikainen, Miina and Broatch, James and Zarekookandeh, Navabeh and Hanson, Ola and Ekström, Ola and Asplund, Olof and Lamon, Séverine and Alexander, Sarah E. and Smith, Cassandra and Bauer, Carlie and Woessner, Mary N. and Levinger, Itamar and Teschendorff, Andrew E. and Gillberg, Linn and Blom, Ida and Helge, Jørn Wulff and Harvey, Nicholas R. and Haupt, Larisa M. and Griffiths, Lyn R. and Deshmukh, Atul S. and Pietiläinen, Kirsi H. and Piirilä, Päivi and Seaborne, Robert A.E. and Klevjer, Marie and Bye, Anja and Wisløff, Ulrik and Jones-Freeman, Bernadette and Eynon, Nir}},
  issn         = {{2639-1856}},
  keywords     = {{CP: Metabolism; DNA methylation; epigenetics; exercise; gene expression; Multi Omics; proteomic; skeletal muscle; transcriptomic; VO}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Molecular landscape of sex- and modality-specific exercise adaptation in human skeletal muscle through large-scale multi-omics integration}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2025.115750}},
  doi          = {{10.1016/j.celrep.2025.115750}},
  volume       = {{44}},
  year         = {{2025}},
}