Epigenetics and aging

Epigenetics may be defined as changes in gene frequencies without alterations in DNA nucleotide sequences. Generally this occurs with DNA methylation or in some cases what is termed hypermethaltion and histdone modifications. As a person ages these epigentic effects are more likely to occur and may lead to the formation of cancerous tumors. A current article, "Epigenetics and aging: the targets and the marks" by Friga and Esteller (2007) in Trends in Genetics has a good overview of aging and and the epigenetics.

‘Aging epigenetics’ is an emerging field that promises exciting revelations in the near future. Here we focus on the functional and biological significance of the epigenetic
alterations that accumulate during aging and are important in tumorigenesis. Paradigmatic examples are provided by the global loss of DNA methylation in aging
and cancer and by the promoter hypermethylation of genes with a dual role in tumor suppression and progeria, such as the Werner syndrome (WRN) and lamin A/C genes. Another twist is provided by sirtuins, a family of NAD-dependent deacetylases that act on Lys16 of histone H4, which are emerging as a link between cellular transformation and lifespan.

As we begin know about the inner workings of the genome, it is interesting proposition to begin to understand how cells age biologically and this has important implications on how we treat complex chronic degenerative disorders (CDDs). If you take the example of Werner syndrome mentioned in this article and the use of MZ twins you find a large genetic component to aging. The interesting facts that this article go into are that the DNA promoter hypermethylation is implicated in a number of CDDs, including cataracts, Type II diabetes, osteoporosis, various forms of arteriosclerosis, hypogonadism, as well as cancer. What this process is doing is turning off genes that have important implications for normal cellular functioning but by effectively shutting down the promoters it causes havoc in the cell. However, a number of questions need to be answered, such as how heritable are traits and what is the influence of environment on the process. Although as with most scientific endeavors the more we find out about these things the less we seem to know.

References Cited

Fraga MF, M Esteller (2007) Epigenetics and aging: the targets and the marks. Trends in Genetics (23) 8, 413-418