title: The role of DNA methylation in aging, rejuvenation, and age-related disease.
abstract: 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.
authors.affiliation: Department of Physiological Sciences, University of Arizona, Tucson, AZ, USA.
authors.forename: Adiv A
authors.initials: AA
authors.lastname: Johnson
authors.forename: Kemal
authors.initials: K
authors.lastname: Akman
authors.forename: Stuart R G
authors.initials: SR
authors.lastname: Calimport
authors.forename: Daniel
authors.initials: D
authors.lastname: Wuttke
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stolzing
authors.forename: João Pedro
authors.initials: JP
authors.lastname: de Magalhães
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D012060:Rejuvenation / Q000502:physiology*
chemical_list: D015254:DNA Modification Methylases