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Age-associated epigenetic drift: implications, and a case of epigenetic thrift?

Teschendorff, AE; West, J; Beck, S; (2013) Age-associated epigenetic drift: implications, and a case of epigenetic thrift? Human Molecular Genetics , 22 (R1) R7-R15. 10.1093/hmg/ddt375. Green open access

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Abstract

It is now well established that the genomic landscape of DNA methylation gets altered as a function of age, a process we here call "epigenetic drift". The biological, functional, clinical and evolutionary significance of this epigenetic drift however remains unclear. We here provide a brief review of epigenetic drift, focusing on the potential implications for ageing, stem-cell biology and disease risk prediction. It has been demonstrated that epigenetic drift affects most of the genome, suggesting a global deregulation of DNA methylation patterns with age. A component of this drift is tissue specific, allowing remarkably accurate age-predictive models to be constructed. Another component is tissue-independent, targeting stem-cell differentiation pathways and affecting stem cells, which may explain the observed decline of stem cell function with age. Age-associated increases in DNA methylation target developmental genes, overlapping those associated with environmental disease risk factors and with disease itself, notably cancer. In particular, cancers and precursor cancer lesions exhibit aggravated age DNA methylation signatures. Epigenetic drift is also influenced by genetic factors. Thus, drift emerges as a promising biomarker for premature or biological ageing, and could potentially be used in geriatrics for disease risk prediction. Finally, we propose, in the context of human evolution, that epigenetic drift may represent a case of epigenetic thrift, or bet-hedging. In summary, this review demonstrates the growing importance of the "ageing epigenome", with potentially far reaching implications for understanding the effect of age on stem cell function and differentiation, as well as for disease prevention.

Type: Article
Title: Age-associated epigenetic drift: implications, and a case of epigenetic thrift?
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/hmg/ddt375
Publisher version: http://dx.doi.org/10.1093/hmg/ddt375
Language: English
Additional information: © The Author 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1401357
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