Question

Discuss how aging in mice is reflected in the methylation status of DNA

Answer 1

Additionally, several studies have characterized the effects of aging across the methylome in a wide variety of tissues from humans and mice. ... Therefore, while only a small fraction of cytosines in the genome show changes in DNA methylation with age, this represents 2 to 3 million cytosines in the genome.

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

the mouse methylation clock is affected by biological interventions and as such we suggest that the prediction of the clock reflects not only chronological age but also biological age. It will be exciting to test the consequences of manipulations of the ticking rate of the epigenetic clock on biological function, in particular the possible reversibility of ageing associated functional decline. We believe that this work will help scientists gain insights into the biology of ageing and potentially help to discover novel strategies to extend lifespan and health span in the future.