P 023

Ageing is associated with a shift in normal patterns of DNA methyla-tion, including increased methylation of CpG islands. This may have significant effects on gene expression and could, in part, underlie the strong association between ageing and human disease. To study the extent and variability of age-associated methylation, we have studied peripheral blood leukocyte (PBL) DNA samples from 490 participants in the Newcastle 85+ study. DNA methyla-tion at the promoter region of 15 candidate genes was quantified using Pyrosequencing. This analysis detected frequent, highly variable methylation (1-41% CpG sites methylated), including genes known to be expressed and with apparently important biological roles (e.g. tumour-suppressor candidates TWIST2, TUSC3). Genes susceptible to variable methyla-tion corresponded to those known to be methylated in malignancies derived from PBL, but not those methylated in other cancer types (e.g. MLH1). Genes displaying age-related methylation were also strongly co-methylated, akin to the CIMP phenotype found in cancer. Bisulfite sequencing identified the presence of leukaemia-like densely methylated alleles. Participants with a previous history of cancer or who subsequently developed cancer had significantly higher methylation than cancer-free participants. Increased methylation was also associated with increased frailty and methylation of a specific locus (EPHA10) was significantly and reproducibly associated with dementia. The results demonstrate extensive and variable methylation in the elderly, imply the existence of a common mechanism for age-related and cancer-related methylation and identify significant associations with age-related disease.