Comparative analysis of acute eccentric contraction-induced changes to the skeletal muscle transcriptome in young and aged mice and humans

Adaptations to skeletal muscle following resistance exercise are due in part to changes to the skeletal muscle transcriptome. Although transcriptional changes in response to resistance exercise occur in young and aged muscles, aging alters this response. Rodent models have served great utility in defining regulatory factors that underscore the influence of mechanical load and aging on changes to skeletal muscle phenotype. Unilateral eccentric contractions in young and aged rodents are widely used to model resistance exercises in humans. However, the extent to which unilateral eccentric contractions in young and aged rodents mimic the transcriptional response in humans remains unknown. We reanalyzed two publicly available RNA sequencing datasets from young and aged mice and humans that were subjected to acute eccentric contractions to define key similarities and differences in the muscle transcriptional response following this exercise modality. The effect of aging on the number of contraction-sensitive genes, the distribution patterns of those genes into unique/common categories, and the cellular pathways associated with the differentially expressed genes (DEGs) were similar in mice and humans. However, there was little overlap between species when comparing specific contraction-sensitive DEGs within the same age group. There were strong intraspecies relationships for the common transcription factors predicted to influence the contraction-sensitive gene sets, whereas interspecies relationships were weak. Overall, these data demonstrate key similarities between mice and humans for the contraction-induced changes to the muscle transcriptome, but we posit species-specific responses exist and should be taken into consideration when attempting to translate rodent eccentric exercise models.<b>NEW & NOTEWORTHY</b> Acute eccentric muscle contractions in rodents are used to model resistance exercise in young and aged humans, including changes to the muscle transcriptome. This work defines the utility of the rodent model at mimicking the transcriptional features observed in young and aged humans.