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.