Temporal multi-omic analysis uncovers sex-biased molecular programs underlying skeletal muscle adaptation to endurance training.

Authors

Gina M Many, Christopher Jin, Nicholas J Day, Gayatri Iyer, Gregory Smith, Kayleigh Voos, James A Sanford, Akshay Bareja, David Jimenez-Morales, Damon T Leach, Tyler J Sagendorf, Abdalla Ahmed, Xiaolu Li, Matthew J Gaffrey, Isaac K Attah, Hugh D Mitchell, Mark R Viggars, David Gaul, Kim M Huffman, Facundo Fernández, Michael P Snyder, Eric Ortlund, Wendy Kohrt, Matthew T Wheeler, William E Kraus, Karyn A Esser, Bret H Goodpaster, Laurie J Goodyear, Charles F Burant, Christopher B Newgard, Andrea L Hevener, Sue C Bodine, Wei-Jun Qian, Simon Schenk, Joshua N Adkins, Malene E Lindholm, MoTrPAC study group

Published in

Cell reports. Volume 45. Issue 8. Pages 117823. Aug 12, 2026. Epub Aug 12, 2026.

Abstract

Exercise training confers broad health benefits, yet molecular regulators of skeletal muscle adaptation, particularly sex-specific mechanisms, remain incompletely understood. Integrating new and previously published multi-omics data from the molecular transducers of physical activity consortium (MoTrPAC), we characterized metabolomic, epigenomic, transcriptomic, proteomic, and post-translational modification (PTM) responses to 1-8 weeks of endurance exercise training in male and female rat gastrocnemius. While transcriptomic and proteomic responses were largely sex-concordant, there were distinct sex-specific training-induced PTM signatures, particularly in the redox proteome. Females exhibited decreased mitochondrial protein cysteine oxidation alongside increased oxidation of glycolytic proteins relative to males, suggesting sex-biased subcellular reactive oxygen species (ROS) dynamics. Multi-omic factor analysis (MOFA) identified coordinated sex-concordant molecular programs and further supported female-specific mechanisms of redox buffering with training. Together, these findings indicate that sex-specific skeletal muscle exercise adaptations are particularly evident at the PTM level in rats, and identify future avenues for precision exercise health and medicine.

PMID:
42585023
Bibliographic data and abstract were imported from PubMed on 13 Aug 2026.

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