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

Adiv A. Johnson, Kemal Akman, Stuart R.G. Calimport, Daniel Wuttke, Alexandra Stolzing*, João Pedro de Magalhães

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)483-494
Number of pages12
JournalRejuvenation research
Volume15
Issue number5
DOIs
Publication statusPublished - 25 Oct 2012

Fingerprint

Rejuvenation
Methyltransferases
DNA Methylation
DNA
Epigenomics
Hereditary Sensory and Autonomic Neuropathies
5-Methylcytosine
Azacitidine
Cytosine
Gene Silencing
Osteoarthritis
Methionine
Methylation
Dementia
Neoplasms
Carbon
Biomarkers
Clinical Trials
Genome
Pathology

Cite this

Johnson, A. A., Akman, K., Calimport, S. R. G., Wuttke, D., Stolzing, A., & de Magalhães, J. P. (2012). The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation research, 15(5), 483-494. https://doi.org/10.1089/rej.2012.1324
Johnson, Adiv A. ; Akman, Kemal ; Calimport, Stuart R.G. ; Wuttke, Daniel ; Stolzing, Alexandra ; de Magalhães, João Pedro. / The role of DNA methylation in aging, rejuvenation, and age-related disease. In: Rejuvenation research. 2012 ; Vol. 15, No. 5. pp. 483-494.
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Johnson, AA, Akman, K, Calimport, SRG, Wuttke, D, Stolzing, A & de Magalhães, JP 2012, 'The role of DNA methylation in aging, rejuvenation, and age-related disease', Rejuvenation research, vol. 15, no. 5, pp. 483-494. https://doi.org/10.1089/rej.2012.1324

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; de Magalhães, João Pedro.

In: Rejuvenation research, Vol. 15, No. 5, 25.10.2012, p. 483-494.

Research output: Contribution to journalArticle

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Johnson AA, Akman K, Calimport SRG, Wuttke D, Stolzing A, de Magalhães JP. The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation research. 2012 Oct 25;15(5):483-494. https://doi.org/10.1089/rej.2012.1324