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Chicken and the Egg: Physical Activity and Epigenetics


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Medicine & Science in Sports & Exercise: March 2020 - Volume 52 - Issue 3 - p 588
doi: 10.1249/MSS.0000000000002176
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It is well accepted that epigenetic mechanisms—those mechanisms arising from environmental factors external to the cell that alter gene expression without altering the underlying DNA (1)—play critical roles in the regulation of many physiological pathways. Earlier this year, in one of the first studies of its kind, van Roekel and colleagues (2) showed that physical activity levels were associated with methylation at one DNA CpG site, with weaker associations for 14 other CpG sites. However, it was unclear if these methylation sites were involved in regulating physical activity or were regulated by physical activity.

As such, it is significant that two studies in this issue, Fernandez-Sanles et al. (3) and Wu et al. (4), continue to work in this area and address the relationship between epigenetic factors and physical activity.

Fernandez-Sanles and colleagues (3) used a two-stage study to determine the “association between physical activity and genome-wide DNA methylation.” They estimated physical activity from a validated questionnaire and sampled genomic DNA from 619 individuals in an untargeted methylation study to establish associations between physical activity and methylation of CpG sites. Importantly, Fernandez-Sanles and colleagues then validated the significant CpG sites found in the untargeted stage of the study in two independent populations that totaled over 1900 subjects. As a result, Fernandez-Sanles et al. (3) found and validated two CpG sites associated with physical activity. Although it is unclear if these methylated CpG site were due to the physical activity of the subjects or if they were inherent and regulated physical activity, the results begin to lay a foundation of CpG sites associated with physical activity.

Taking a different approach, Wu and colleagues (4) investigated in a targeted manner whether there were epigenetic changes associated with hormone status and physical activity (determined by wrist-worn accelerometers) in a cohort of 519 young teenagers. Specifically, Wu and colleagues examined DNA methylation of the growth-related genes HSD11B2 and H19, as well as in the long-interspersed nucleotide (LINE-1) repeats which have recently been shown to be involved in other exercise responses (5). As a result, Wu and colleagues showed a sex difference in methylation of H19 and LINE-1 with no association between methylation and physical activity. However, physical activity did increase methylation of HSD11B2 by almost sixfold in this young cohort, suggesting, in this case, that physical activity can serve as an epigenetic initiator in young teenagers. This result is important because it suggests that routine physical activity can serve to alter gene expression in some growth-related genes through epigenetic mechanisms.

Thus, although it is still unclear whether epigenetic changes are a regulating factor for daily physical activity, just a consequence of physical activity, or both, these two studies, along with the studies by van Roekel et al. (2) and Roberson et al. (5) provide the initial foundation upon which to begin to tease out the interrelated role of epigenetics and daily physical activity.

J. Timothy Lightfoot
Texas A&M University
College Station, TX


1. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev. 2009;23(7):781–3.
2. Van Roekel EH, Dugué PA, Jung CH, et al. Physical activity, television viewing time, and DNA methylation in peripheral blood. Med Sci Sports Exerc. 2019;51(3):490–8.
3. Fernández-Sanlés A, Sayols-Baixeras S, Castro De Moura M, et al. Physical activity and genome-wide DNA methylation: the REgistre GIroní del COR study. Med Sci Sports Exerc. 2020;52(3):589–97.
4. Wu Y, Goodrich JM, Dolinoy DC, et al. Accelerometer-measured physical activity, reproductive hormones and DNA methylation. Med Sci Sports Exerc. 2020;52(3):598–607.
5. Roberson PA, Romero MA, Osburn SC, et al. Skeletal muscle LINE-1 ORF1 mRNA is higher in older humans but decreases with endurance exercise and is negatively associated with higher physical activity. J Appl Physiol (1985). 2019;127(4):895–904.
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