Differential Response Trajectories to Acute Exercise in Blood and Muscle

Human physical performance, a critical determinant of human survival over thousands of years, is among the most potent medical interventions. However, the molecular mechanisms that drive exercise adaptation are incompletely understood. We created a computational framework comprising data from 49 studies, including 1,986 individuals before and after acute exercise and long-term training from skeletal muscle (n=1,260) and blood (n=726). This is the largest framework of its kind.  Using a linear mixed effects meta-regression model selection strategy, we detected specific time patterns and novel regulatory modulators of the acute exercise response. We found that acute and long-term responses to exercise are transcriptionally distinct. Exercise induced a more pronounced inflammatory response in skeletal muscle of older individuals and our models revealed multiple sex-associated responses to training. These results deepen our understanding of the transcriptional responses to exercise and provide a powerful resource for future research efforts in exercise physiology and medicine.