Molecular Landscape of Modality-Specific Exercise Adaptation in Human Skeletal Muscle through Large-Scale Multi-OMICs Integration

Macsue Jacques; Shanie Landen; Adam Philip Sharples; ANDREW P. GARNHAM; Ralf B. Schittenhelm; Joel Stele; Aino Heikkinen; Elina Sillanpää; Miina Ollikainen; James R. Broatch; Navabeh Zarekookandeh; Ola Hanson; Ola Ekström; Olof Asplund; Séverine Lamon; Sarah E. Alexander; Cassandra Smith; Carlie Bauer; Mary N. Woessner; Itamar Levinger; Andrew Erich Teschendorff; Linn Gillberg; Ida Blom; Jørn Wulff Helge; Nicholas R. Harvey; Larisa Margaret Haupt; Lyn Robyn Griffiths; Atul S. Deshmukh; Kirsi Hannele Pietiläinen; Päivi Liisa Piirilä

doi:10.1101/2024.07.14.603458

Molecular BiologybioRxivJul 14, 2024

Preprint

Molecular Landscape of Modality-Specific Exercise Adaptation in Human Skeletal Muscle through Large-Scale Multi-OMICs Integration

Macsue Jacques iD, Shanie Landen iD, Adam Philip Sharples iD, ANDREW P. GARNHAM iD, Ralf B. Schittenhelm iD, Joel Stele, Aino Heikkinen iD, Elina Sillanpää iD, Miina Ollikainen iD, James R. Broatch iD, Navabeh Zarekookandeh iD, Ola Hanson, Ola Ekström iD, Olof Asplund iD, Séverine Lamon iD, Sarah E. Alexander iD, Cassandra Smith iD, Carlie Bauer iD, Mary N. Woessner iD, Itamar Levinger iD, Andrew Erich Teschendorff iD, Linn Gillberg iD, Ida Blom iD, Jørn Wulff Helge iD, Nicholas R. Harvey iD, , Nir Eynon iD

Abstract

We conducted a large-scale, statistically powered, meta-analysis of exercise adaptations in human skeletal muscles, integrating epigenetic, transcriptomic, transcription factors, and proteomic data across 12 independent cohorts comprising over 1000 participants and 2340 human muscle samples. Our study identified distinctive signatures associated with maximal oxygen consumption (VO2max), and identified five genes robustly intersecting multi-OMIC layers. Notably, transcription factors predominantly functioned as activators across these layers, regulating expression of target genes irrespective of whether DNA methylation levels were low or high, indicating a synergistic effect between TFs and the methylome. Analysis of distinct exercise modalities (aerobic and resistance exercise) revealed unique gene pathways, contrasting with patterns observed in inactivity (muscle disuse) studies. These findings offer a comprehensive understanding of exercise and modality-specific adaptations, shedding light on muscle health and the molecular mechanisms associated with cardiorespiratory fitness, aging, and disease prevention.

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