Author Identifier

Cassandra Smith: https://orcid.org/0000-0002-2517-2824

Document Type

Journal Article

Publication Title

Cell Reports

Volume

44

Issue

6

Publisher

Elsevier

School

Nutrition and Health Innovation Research Institute

Funders

National Health and Medical Research Council / Hevolution/AFAR New Investigator Awards in Aging Biology and Geroscience Research / Australian Research Council / Novo Nordisk Foundation (NNF18CC0034900, NNF14CC001, NNF20OC0060547, NNF17OC0027232, NNF10OC1013354) / Research Council of Finland (335443, 314383, 272376, 266286, 328685, 307339, 297908, 251316) / Finnish Medical Foundation / Gen Foundation / Finnish Diabetes Research Foundation / Paulo Foundation / University of Helsinki and Helsinki University Hospital / Sigrid Jusélius Foundation / Minerva Foundation

Grant Number

NHMRC Number : APP1194159, ARC Numbers : DP190103081, DP200101830, DP240102155

Comments

Jacques, M., Landen, S., Sharples, A. P., Garnham, A., Schittenhelm, R., Steele, J., Heikkinen, A., Sillanpää, E., Ollikainen, M., Broatch, J., Zarekookandeh, N., Hanson, O., Ekström, O., Asplund, O., Lamon, S., Alexander, S. E., Smith, C., Bauer, C., Woessner, M. N., . . . Eynon, N. (2025). Molecular landscape of sex- and modality-specific exercise adaptation in human skeletal muscle through large-scale multi-omics integration. Cell Reports, 44(6), 115750. https://doi.org/10.1016/j.celrep.2025.115750

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 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.

DOI

10.1016/j.celrep.2025.115750

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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Link to publisher version (DOI)

10.1016/j.celrep.2025.115750