Mather, Armstrong, Thalamuthu & Kwok Keywords: DNA methylation • epigenetic clock • exceptional longevity • longitudinal studies

With the advancement in science and technology, many clues are available, but not enough to have a clear picture of how DNA methylation loci are associated with “exceptional aging”.

There are two factors that are considered as causes of aging. One is the concept of entropy, where disorder accumulates and bodily parts wear out over time. Another is that aging happens according to an instruction set written in the genome. ¹⁾ Related to the hypothesis that aging has a programmed component, is epigenetics.

“Epigenetics is the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself.” ²⁾ Older persons express the same genes differently than a younger person. DNA contains the genetic code for both states, both young and old.

Gene expression can be altered by many means, including histone acetylation, chromatin remodeling, noncoding RNAs, and DNA methylation. DNA methylation has had the most study due to the ease in which it can be investigated, and is the focus of the article.

“DNA methylation is the process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence.” ³⁾

An organism can create a molecule used for its sustenance, by copying a segment of the DNA molecule as an RNA molecule, a process known as transcription. Transcription is affected by methylation.

Methylation can have many effects, depending on its location. Effects include disabling or slowing down transcription, therefore decreasing the supply of the particular molecule.

Because of the complexity of molecular interactions in an organism, cause and effect are difficult to establish. The article covers many other research studies trying to find patterns between methylation, health, and age. Research has hypothesized the existence of an epigentic clock that may be based on the methylation state.