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

Johnson, Adiv A., Akman, Kemal, Calimport, Stuart R.G., Wuttke, Daniel, Stolzing, Alexandra and de Magalhães, João Pedro (2012). The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation research, 15 (5), pp. 483-494.


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.

Publication DOI:
Divisions: Life & Health Sciences > Pharmacy
Uncontrolled Keywords: Ageing,Geriatrics and Gerontology
Full Text Link: http://europepm ... 48&blobtype=pdf
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://online.l ... 9/rej.2012.1324 (Publisher URL)
Published Date: 2012-10-25
Authors: Johnson, Adiv A.
Akman, Kemal
Calimport, Stuart R.G.
Wuttke, Daniel
Stolzing, Alexandra
de Magalhães, João Pedro

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