The role of DNA methylation and hydroxymethylation in immunosenescence

A healthy functioning immune system is critical to stave off infectious diseases, but as humans and other organisms age, their immune systems decline. As a result, diseases that were readily thwarted in early life pose nontrivial harm and can even be deadly in late life. Immunosenescence is defined as the general deterioration of the immune system with age, and it is characterized by functional changes in hematopoietic stem cells (HSCs) and specific blood cell types as well as changes in levels of numerous factors, particularly those involved in inflammation. Potential mechanisms underlying immunosenescence include epigenetic changes such as changes in DNA methylation (DNAm) and DNA hydroxymethylation (DNAhm) that occur with age. The purpose of this review is to describe what is currently known about the relationship between immunosenescence and the age-related changes to DNAm and DNAhm, and to discuss experimental approaches best suited to fill gaps in our understanding.