| Title: |
The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease |
| Authors: |
Johnson, Adiv A.; Akman, Kemal; Calimport, Stuart R.G.; Wuttke, Daniel; Stolzing, Alexandra; de Magalhães, João Pedro |
| Source: |
Rejuvenation Research ; volume 15, issue 5, page 483-494 ; ISSN 1549-1684 1557-8577 |
| Publisher Information: |
SAGE Publications |
| Publication Year: |
2012 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1089/rej.2012.1324 |
| Availability: |
https://doi.org/10.1089/rej.2012.1324; https://journals.sagepub.com/doi/full-xml/10.1089/rej.2012.1324; https://journals.sagepub.com/doi/pdf/10.1089/rej.2012.1324 |
| Rights: |
https://journals.sagepub.com/page/policies/text-and-data-mining-license |
| Accession Number: |
edsbas.E29F06A0 |
| Database: |
BASE |