Comparing changes to the skeletal muscle transcriptome of young and aged mice to young and aged humans in response to acute eccentric contractions

Resistance exercise alters several molecular events in skeletal muscle that change muscle size and function, including changes to the transcriptome. The signals altering the muscle transcriptome in response to resistance exercise remain ill defined. Defining those regulatory signals in muscle requires non-human models where manipulations can assess cause and effect. The electrically induced, unilateral eccentric contraction model of resistance exercise in rodents is widely used to mimic resistance exercise. However, the transcriptional changes that occur in response to eccentric contractions in the rodent model and the continuity of the rodent model to resistance exercise in humans are not well known. The purpose of this study was to define the transcriptional changes in skeletal muscle that occur in response to acute eccentric contractions in young and aged mice and define their continuity to transcriptional changes in the muscle of young and aged humans. Four-month-old and 24-month-old male C57BL/6 mice were subjected to a bout of electrically induced, unilateral eccentric contractions of the tibialis anterior (TA) muscle. RNA was isolated from the TA and subjected to RNA Sequencing. Lists of differentially expressed genes (DEGs) from the TA of young and aged mice were compared to RNA Sequencing datasets generated from the vastus lateralis muscle of young and aged humans following acute eccentric contractions. L andscape I n S ilico deletion A nalysis (Lisa) was used to predict the magnitude of transcription factor regulation of the DEGs. DEGs for mice or humans were categorized into age specific DEGs (specific to young or aged) or DEGs shared by both ages. The number of DEGs for mice or humans were distributed equally to each category, showing an age specific distribution that was conserved in both mice and humans. However, the DEGs in young and aged mice had very little overlap to the DEGs in young and aged humans. Only 113 DEGs were common across all ages and species. Interestingly, the relationship of transcription factors predicted to regulate DEGs between young and aged mice or young and aged humans was very strong. However, the relationship of transcription factors predicted to regulate DEGs of young mice and young humans or aged mice and aged humans was rather weak. In all, these data highlight the consistencies and differences in the muscle transcriptomic response to eccentric contractions. This work was supported in part by NIH R03AG073445 (BSG). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.