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

Lookup NU author(s): Dr Joanna Collerton, Hannah Gautrey, Sanne van Otterdijk, Dr Karen Davies, Dr Carmen Martin-RuizORCiD, Professor Thomas von Zglinicki, Emeritus Professor Thomas Kirkwood, Emerita Professor Carol Jagger, Professor John Mathers, Dr Gordon Strathdee



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


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.

Publication metadata

Author(s): Collerton J, Gautrey HE, van Otterdijk SD, Davies K, Martin-Ruiz C, von Zglinicki T, Kirkwood TBL, Jagger C, Mathers JC, Strathdee G

Publication type: Article

Publication status: Published

Journal: Biogerontology

Year: 2014

Volume: 15

Issue: 4

Pages: 317-328

Print publication date: 01/08/2014

Online publication date: 26/04/2014

Acceptance date: 01/04/2014

Date deposited: 26/11/2014

ISSN (print): 1389-5729

ISSN (electronic): 1573-6768

Publisher: Springer Netherlands


DOI: 10.1007/s10522-014-9500-9


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Funder referenceFunder name
Biotechnology and Biological Sciences Research Council
Newcastle Healthcare Charity
National Institute for Health Research Newcastle Biomedical Research Centre
Newcastle Healthcare Charity and Newcastle upon Tyne hospitals NHS Charity
UK Medical Research Council
G0500997Biotechnology and Biological Sciences Research Council
R124/0509Dunhill Medical Trust