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The role of DNA methylation in aging, rejuvenation, and age-related disease

journal contribution
posted on 2015-02-26, 09:41 authored by Adiv A. Johnson, Kemal Akman, Stuart R.G. Calimport, Daniel Wuttke, Alexandra StolzingAlexandra Stolzing, Joao Pedro De Magalhaes
DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-l-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation. © Copyright 2012, Mary Ann Liebert, Inc. 2012.

Funding

The authors thank Daniel Kimbel and Bryan Vukorepa for collaborative interactions and helpful discussions. J.P.M. is grateful to the BBSRC, the Wellcome Trust, the Ellison Medical Foundation, and a Marie Curie International Reintegration Grant within EC-FP7 for supporting work in his laboratory.

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Published in

Rejuvenation Research

Volume

15

Issue

5

Pages

483 - 494

Citation

JOHNSON, A.A. ... et al., 2012. The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation Research, 15 (5), pp. 483 - 494.

Publisher

© Mary Ann Liebert, Inc.

Version

  • VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2012

Notes

Closed access. Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/rej.2012.1324

ISSN

1549-1684

eISSN

1557-8577

Language

  • en

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