Exercise effects on methylation of ASC gene.
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-1beta and IL-18 secretion, were investigated by ASC gene methylation. Further, the relationship between carcinogenesis and exercise, and methylation of the P15 tumor suppressive gene was also analyzed. High-intensity interval walking exercise, consisting of 3 min low-intensity walking at 40% of peak aerobic capacity followed by a 3 min 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<0.01), 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<0.01), 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.
Nakajima
K
K
Department of Molecular Oncology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Takeoka
M
M
Mori
M
M
Hashimoto
S
S
Sakurai
A
A
Nose
H
H
Higuchi
K
K
Itano
N
N
Shiohara
M
M
Oh
T
T
Taniguchi
S
S
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D053468:CARD Signaling Adaptor Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D019175:DNA Methylation / Q000502:physiology*; D044127:Epigenesis, Genetic; D015444:Exercise / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA / Q000379:methods; D016138:Walking / Q000502:physiology; D055815:Young Adult
D053468:CARD Signaling Adaptor Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D003598:Cytoskeletal Proteins; C402202:PYCARD protein, human