Acquisition of aberrant DNA methylation is associated with frailty in the very old: findings from the Newcastle 85+Study

作者：Collerton Joanna; Gautrey Hannah E; van Otterdijk Sanne D; Davies Karen; Martin Ruiz Carmen; von Zglinicki Thomas; Kirkwood Thomas B L; Jagger Carol; Mathers John C; Strathdee Gordon^*

来源：Biogerontology, 2014, 15(4): 317-328.

DOI：10.1007/s10522-014-9500-9

• Ageing
• Frailty
• DNA methylation
• CpG island
• Epigenetics

Frailty is a major health problem in older people and, as the population ages, identification of its underlying biological mechanisms will be increasingly important. DNA methylation patterns within genomic DNA change during ageing and alterations in DNA methylation, particularly at gene promoter regions, can lead to altered gene expression. However the importance of altered DNA methylation in frailty is largely unknown. Using cross-sectional data from the Newcastle 85+ Study (all participants aged 85 years) frailty was operationalized by the Fried model. DNA methylation levels were assessed by highly quantitative pyrosequencing at the gene promoter associated CpG islands from a panel of five age-related methylation marker loci and at LINE-1 repetitive elements (as a surrogate for genome-wide methylation). While genome-wide methylation (as assessed at LINE-1 elements) showed no association with frailty status, there was a clear association between CpG island methylation and frailty. When compared to participants with CpG island methylation levels in the combined middle two (referent) quartiles, those in the lowest quartile had significantly decreased odds of frailty [odds ratio 0.47 (95 % CI 0.26-0.85); n = 321, p = 0.013]. Overall this study suggests a potential role for age-related changes in CpG island methylation in the development of frailty.

• 出版日期2014-8