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

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Abstract

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.

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Acknowledgments

Thanks are especially due to the 85 year olds of Newcastle and North Tyneside, and their families and carers, for the generous donation of their time and personal information to make the study possible. In addition we thank the: research nurses (Brenda Balderson, Sally Barker, Julie Burrows, June Edwards, Julie Ferguson, Gill Hedley, Joan Hughes, Judith Hunt, Julie Kimber and Victoria Raynor); biomarker technicians (Sam Jameson, Claire Kolenda, Craig Parker and Anna Tang); data manager (Pauline Potts); project secretary (Lucy Farfort); and the North of England Commissioning Support Unit (formerly NHS North of Tyne, working on behalf of Newcastle and North Tyneside Primary Care Trusts and Northumberland Care Trust) and local general practices. The Newcastle 85+ Study was funded by a combined grant from the UK Medical Research Council and the Biotechnology and Biological Sciences Research Council (G0500997), the Dunhill Medical Trust (R124/0509), and a grant from the Newcastle Healthcare Charity. The research was also supported by the National Institute for Health Research Newcastle Biomedical Research Centre, based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. HG was funded by a PhD studentship from the Biotechnology and Biological Sciences Research Council and SvO was funded by a PhD studentship from the National Institute for Health Research Newcastle Biomedical Research Centre and a project grant from the Newcastle Healthcare Charity and Newcastle upon Tyne hospitals NHS Charity.

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Authors and Affiliations

  1. Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK

    Joanna Collerton, Karen Davies, Carmen Martin-Ruiz, Thomas von Zglinicki, Thomas B. L. Kirkwood & Carol Jagger

  2. Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE1 4LP, UK

    Hannah E. Gautrey, Sanne D. van Otterdijk & Gordon Strathdee

  3. Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK

    John C. Mathers

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  1. Joanna Collerton
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Correspondence to Gordon Strathdee.

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Joanna Collerton and Hannah E. Gautrey have contributed equally to this work.

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Collerton, J., Gautrey, H.E., van Otterdijk, S.D. et al. Acquisition of aberrant DNA methylation is associated with frailty in the very old: findings from the Newcastle 85+ Study. Biogerontology 15, 317–328 (2014). https://doi.org/10.1007/s10522-014-9500-9

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