2134/16821 Adiv A. Johnson Adiv A. Johnson Kemal Akman Kemal Akman Stuart R.G. Calimport Stuart R.G. Calimport Daniel Wuttke Daniel Wuttke Alexandra Stolzing Alexandra Stolzing Joao Pedro De Magalhaes Joao Pedro De Magalhaes The role of DNA methylation in aging, rejuvenation, and age-related disease Loughborough University 2015 untagged Mechanical Engineering not elsewhere classified 2015-02-26 09:41:44 Journal contribution https://repository.lboro.ac.uk/articles/journal_contribution/The_role_of_DNA_methylation_in_aging_rejuvenation_and_age-related_disease/9545006 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.