Decoupling of DNA Methylation Status and Gene Expression Levels in Aging Individuals

Aging is a multi-factorial process, where epigenetic factors play one of the major roles in declines of gene expression and organic function. DNA methylation at CpG islands of promoters can directly change the expression of the neighbouring gene mostly through inhibition. Furthermore, it is known that DNA methylation patterns change during aging In our study, we investigated gene regulation through DNA methylation of genes up- and downregulated in long-lived people compared to a younger cohort. Our data revealed that comparatively highly methylated genes were associated with high expression in long-lived people (e.g. over 85). Genes with lower levels of methylation were associated with low expression. These findings might contradict the general model used to associate methylation status with expression. Indeed, we found that methylation in the promoter regions of all investigated genes is rather constant across different age groups, meaning that the disparity between methylation and expression only happens in older people. A potential explanation could be the impact of other epigenetic mechanisms, possibly related to stress.