Exercise Effects on Methylation ofASCGene

Abstract

Chronic moderate exercise has been reported to reduce pro-inflammatory cytokines. To analyze the molecular mechanisms by which training exerts these effects, the epigenetic influences of age and exercise on the ASC gene, which is responsible for IL-1β and IL-18 secretion, were investigated by ASC gene methylation. Further, the relationship between carcinogenesis and exercise, methylation of the p15 tumor suppressive gene was analyzed as well. High-intensity interval walking exercise, consisting of 3-minute low-intensity walking at 40% of peak aerobic capacity followed by a 3-minute high-intensity walking period above 70% of peak aerobic capacity, was continued for 6 months. Peripheral blood DNA extracts from young control (n=34), older control (n=153), and older exercise (n=230) groups were then analyzed by pyrosequencing for DNA methylation. Methylation of ASC decreased significantly with age (young control vs. older control, p<.01), which is indicative of an age-dependent increase in ASC expression. Compared to the older control group, the degree of ASC methylation was higher in the older exercise group (older control vs. older exercise:, p<.01) and presumably lower ASC expression. Neither exercise nor age affected the methylation of the p15. In summary, chronic moderate exercise appears to attenuate the age-dependent decrease in ASC methylation, implying suppression of excess pro-inflammatory cytokines through reduction of ASC expression.

Role of physical activity in tumor patients and possible underlying mechanisms

“…The duration of these effects vary from reversible short-term effects to long-lasting and generation-spanning effects. Nakajima et al [57] described lower, age-dependent reductions of ASC gene methylation, which encodes for proinflammatory cytokines, in exercising individuals. Further, Zeng et al [91] were able to show that exercise leads to the hypomethylation of a breast cancerspecific tumor supressor gene.…”

Mechanisms of association between physical functioning and breast cancer mortality: evidence from the Women’s Healthy Eating and Living Study

“…Specifically, physical activity and/or weight loss may produce beneficial effects in breast cancer survivors by modulating circulating biomarkers of inflammation; and these effects of lifestyle on biomarkers of inflammation are both biologically plausible and supported by epidemiologic evidence. For example, a randomized controlled trial conducted by Nakajima and colleagues demonstrated that a 6-month high-intensity walking program (26 min of interval walking training, a minimum of 2 days per week) can lead to an increase in methylation of a gene known to secrete proinflammatory cytokines [33]. Consistent with this biological support, epidemiological studies in breast cancer populations have noted evidence of a protective effect of physical activity on inflammation.…”

Proceedings of the 5th annual symposium of the German Society for Paleo Nutrition held in 2017

“…Thirdly, it was speculated that exercise influences intratumoral angiogenesis [28]. Research of the past decade suggests, that some of the mentioned effects of PA are driven by exercise-induced epigenetic modifications [29,30]. However, most of these results are derived from animal models and need to be confirmed in prospective clinical trials.…”