The Benefits of Exercise Goes Epigenome-Deep

Twin study shows an epigenetic correlation between physical activity and metabolic disease

Not everyone likes to exercise, but let’s face it, exercise is essential for good health. In addition to keeping weight in check, it helps combat many physical and mental disorders. Numerous studies have attested to the benefits of exercise, providing data supporting its role in preventing and managing conditions like heart disease, diabetes, cancer, depression, and anxiety.

So then, why isn’t exercise something we all do regularly? Some say we live in an “obesogenic” world, where inactivity is more or less encouraged. From our sitting jobs to couch potato lifestyles, it’s no wonder that a large portion of the population is overweight. Therefore, to better understand why physical activity is important, some scientists are looking further into how exercise affects the body on a molecular level.

One such research group comes from Washington State University (WSU), where their most recent paper on the subject has been published in the November issue of Scientific Reports. The study, which was conducted on identical twins, found that certain epigenetic molecular factors linked physical activity (PA) to reduced pathologies associated with obesity and metabolic diseases.

Because identical twins share the same genetic code, they make ideal subjects for investigating epigenetic occurrences, which are primarily influenced by environmental exposure rather than genetics. Here, the team measured metabolic syndrome indicators and found that the disease risk of the more physically active twin was lower.

“The findings provide a molecular mechanism for the link between physical activity and metabolic disease,” said WSU biologist and author Michael Skinner. “Physical exercise is known to reduce the susceptibility to obesity, but now it looks like exercise through epigenetics is affecting a lot of cell types, many of them involved in metabolic disease.”

For the study, the researchers collected buccal cells from the cheek area of about 70 identical twins who participated in an exercise study through the Washington State Twin Registry. Data collection was conducted at several different points throughout the study from 2012 to 2019. The twins were given fitness trackers to measure their PA, and metabolic parameters such as body mass index (BMI) and waist circumference were also recorded. In addition, more information was collected from the twins answering survey questions about their living environments, residential communities, and lifestyles.

The results showed that many of the twin pairs differed from each other on measures such as PA, body mass index, and neighborhood walkability (or “walkable” build environments). The WSU Skinner lab further investigated the discordant pairs, where they saw even more differences on an epigenetic level.

Epigenetics can be described as the additional chemical information added to the top of DNA that does not alter the sequential genetic code. This information determines how the genes are read by the cells and may be influenced by various environmental factors such as diet, pollution, stress, and even exercise. The most well-recognized epigenetic mechanism is DNA methylation which involves adding a methyl group to DNA. Typically, DNA methylation will “turn off” gene expression, but it can also be removed through a process called demethylation.

When the Skinner team compared the cheek cells of the discordant twins, they found that the more active siblings (with over 2.5 hours/week of exercise) had alterations in DNA methylation regions (DMRs) associated with reduced BMI and waist size. Prior analyses describe those regions as housing over 50 genes specific to robust PA and metabolic risk factors.

The researchers noted that identical twins might be naturally born genetically the same, but they most often develop different diseases as they age. The only justification for this is epigenetics.

As Skinner explains, “If genetics and DNA sequence were the only driver for biology, then essentially twins should have the same diseases. But they don’t. So that means there has to be an environmental impact on the twins that is driving the development of disease.”

The study clearly points out that PA has an impact on epigenetics and that it correlates with metabolic measures. Although this was expected, the evidence provides direct molecular insights into how the correlation exists – something genome-wide studies fail to do. While more research is needed to uncover the exact mechanisms involved, these findings will hopefully encourage population-wide efforts to create more environments that favor physical, healthy activity.

Source: Glen E. Duncan, et al. Epigenome-wide association study of physical activity and physiological parameters in discordant monozygotic twins. Scientific Reports, November 23, 2022.

Reference: Sara Zaske. Twin study links exercise to beneficial epigenetic changes. Washington State University. December 6, 2022.

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