Background and Purpose-Silent brain infarction (SBI) on MRI is common in elderly people, and recent studies have demonstrated that SBI increases the risk of progression to clinically apparent stroke and cognitive decline. Therefore, an early and accurate detection of SBI and a search for potential treatable risk factors may have a significant impact on public health. Methods-Community-dwelling elderly people aged Ն66 years who participated in the present study (nϭ153) underwent brain MRI and standardized physical and neuropsychological examinations as well as blood biochemistry determinations, including total plasma homocysteine (pHcy), renal function, vitamin status, and polymorphisms of the methylenetetrahydrofolate reductase gene. Results-SBI was found in 24.8% of the participants. In the univariate analysis, the pHcy levels in subjects with SBI (13.6Ϯ4.1 mol/L) were significantly higher (Pϭ0.0004) than those in subjects without SBI (11.0Ϯ3.3 mol/L). When pHcy levels were stratified into high (Ն15.1 mmol/L), moderate (11.6 to 15.0 mmol/L), and low (Յ11.5 mmol/L) groups, age (PϽ0.0001), male sex (PϽ0.0001), the habits of cigarette smoking (PϽ0.0001) and of alcohol consumption (Pϭ0.0002), and folate levels (Pϭ0.01) were significantly associated with an elevation of pHcy levels. The elevated pHcy levels were significantly associated with SBI after individual adjustment for age, sex, hypertension, renal function, and the habits of smoking and alcohol consumption. Conclusions-pHcy level is associated with age and nutritional and other lifestyle factors, and it contributes to a risk for SBI.

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.

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