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.
Document Type
Journal Article
Date of Publication
6-24-2025
Volume
44
Issue
6
Funding Information
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
School
Nutrition and Health Innovation Research Institute
Grant Number
NHMRC Number : APP1194159, ARC Numbers : DP190103081, DP200101830, DP240102155
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Publisher
Elsevier
Identifier
Cassandra Smith: https://orcid.org/0000-0002-2517-2824
Recommended Citation
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., Levinger, I., Teschendorff, A. E., Gillberg, L., Blom, I., Helge, J., Harvey, N., & Haupt, L. M. (2025). Molecular landscape of sex- and modality-specific exercise adaptation in human skeletal muscle through large-scale multi-omics integration. DOI: https://doi.org/10.1016/j.celrep.2025.115750
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