CEND1 and miR885 methylation changes associated with successful cognitive aging in community-dwelling older adults

Age-related cognitive decline (ARCD) leads to deterioration of the quality of life in the elderly. Because emerging evidence suggests age-related illness is associated with gene regulation, it is necessary to understand the factors related to ARCD from an epigenetic perspective to aim for successful cognitive aging (SCA). This study aimed to identify biomarkers for SCA by comparing peripheral blood DNA methylation profiles of community-dwelling older adults with SCA and normal cognitive aging (NCA). We selected 14 SCA participants with scores for all cognitive functions (four domains, namely global cognitive, memory, attention, and executive function) above the average of normative values in Korean older adults and 15 NCA participants from the Korean Frailty Aging Cohort Study (KFACS). We performed methylation microarrays to compare the level of DNA methylation at CpG sites in the SCA and NCA groups. We also validated our findings using gene expression analysis. We found significant differences in eight differentially methylated genes (DMGs)-two hypermethylated genes (IL26 and LOC101060542) and six hypomethylated genes (CEND1, GNAT2, SNORD95, miR885, LOC255167, and HK2). CEND1 (fold change = 5.67) and miR885 (fold change = 8.91) were validated as having significantly different gene expressions between the SCA and NCA groups. Therefore, we postulate them to be potentially promising biomarkers to explain SCA attainment. These findings provide preliminary evidence for understanding SCA and assessing cognitive health in aging.