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Years of Regular Endurance Exercise Leads to Transcriptomic Shifts in Muscles, Study Finds

NEW YORK – Years of running or cycling lead to gene expression shifts in muscle tissue, a new study has found. 

An international team of researchers analyzed the transcriptomes of skeletal muscle samples from adults who underwent endurance or strength training for more than 15 years, which they compared to samples from controls who did not follow such training programs. While exercise has long been known to have health benefits, how physical activity leads to those advantages has been unclear.

Among controls, the researchers noted a number of genes that were differentially expressed between men and women, but that there were fewer differences in gene expression between endurance-trained men and women. They additionally compared the data they generated to a separate cohort of individuals with impaired metabolisms who underwent months-long training to find that after those shorter training times, those individuals' muscle transcriptomes began to resemble those of the long-term endurance-trained individuals. Endurance-trained individuals typically had gene expression changes that affected aerobic metabolism.

"Of note, we observed that endurance training in both women and men drastically alters the transcriptome," researchers led by the Karolinska Institutet's Carl Johan Sundberg wrote in their study, which appeared in Cell Reports on Tuesday.

The researchers collected skeletal muscle biopsies from nine men and nine women who had been undergoing endurance training — such as running or cycling — for at least 15 years and seven men who had been doing strength training — especially movements like squatting and deadlifts — for that same time, and seven male and eight female age-matched controls. 

As expected, the endurance-trained men and women had higher levels of citrate synthase activity and higher proportions of slow-twitch myosin heavy chain (MyHC) I muscle fibers, while the strength-trained men had a higher proportion of fast-oxidative MyHC IIa muscle fibers. 

Following RNA-sequencing to an average depth of 41 million reads, the researchers identified 1,711 genes among endurance-trained women and 1,097 genes among endurance-trained men that were differentially regulated as compared to the matched controls. Both endurance-trained men and women exhibited differences in pathways associated with cellular respiration and tricarboxylic acid metabolism.

Between male and female controls, there were about 450 genes that were differentially regulated, but between endurance-trained men and women, there were fewer differentially regulated genes, about 135, suggesting endurance-trained men and women converge onto a particular skeletal muscle transcriptome.

Meanwhile, the researchers found few genes that were differentially expressed between strength-trained men and untrained controls. This finding suggested to them that changes that arise due to strength training may instead occur at the protein, rather than gene expression, level and that a proteomic analysis is needed. Additionally, they were unable to recruit female strength-trained individuals.

The researchers also combined their findings with those from two other studies that examined gene expression in skeletal muscle in men with type 2 diabetes and in women with metabolic syndrome. At baseline, a number of genes were differentially regulated in opposite directions between the trained and untrained groups. But after a training program of six months or one year, the men with type 2 diabetes and women with metabolic syndrome exhibited gene expression shifts within their skeletal muscle that made them more similar to those of the transcriptomes observed in the long-term trained endurance groups.

"This long-term accumulation of transcriptional changes likely plays a significant role in the health benefits that result from regular physical activity," the researchers wrote.

The researchers cautioned that this study is limited by its cross-sectional nature, rather than being longitudinal, though they noted that approach would likely be prohibitively expensive and ethically questionable if it prevented the control group from regular exercise.