DNA methylation | From the Flight Deck

For several years now I have been hearing “What happens in Vegas stays in Vegas.” A thought-provoking spinoff from this comment is “What happens in Vegas could affect your kids.” Another popular saying: “You are what you eat.” But a more recent and comprehensive statement reads “You are not only what you eat, but what your parents ate.” These recent commentary revisions all relate to the rapidly developing science called epigenetics.

The prefix epi means “on top of” and genome refers to genetic material. And so, the epigenome is situated on top of the genome in the nucleus of the cell. Chemicals, called epigenetic marks, provide basic instructions to the genes, telling them to either switch on or switch off. The genome can be viewed as cellular hardware, while the epigenome can be considered cellular software. The epigenetic changes, either activation or suppression of a gene, are definitely affected by the environment and can be passed on to offspring. Many health problems, ranging from cancer to cardiovascular disease to obesity, can all be caused, in part, by environmental epigenetic-mediated effects on DNA. In the case of cancer, tumor-suppressor genes genetically control cancer by acting as a brake on rapid cancerous cell growth. It is now clear that certain lifestyle choices can result in a change in certain epigenetic marks, which can switch off tumor-suppressor genes. This is called epigenetic silencing and, in this case, if the tumor-suppressing action is switched off, cancer will likely develop.

A fascinating study that focused on the inhabitants of Overkalix, a remote town in northern Sweden, has revealed that environment and lifestyle have a direct impact on future generations. During the early 1900s, there were periods of feast or famine depending on the success or failure of crops in the isolated Overkalix. Young men and women who went from a normal diet to routine overeating during a year of crop success produced children and grandchildren who experienced far shorter lives. The difference in longevity between these offspring and the offspring from parents who had endured a poor harvest was 32 years (1).

Epigenetic changes, which do not involve alterations to the genetic DNA code, are known to have several different mechanisms. One of these mechanisms has been shown to involve the addition of a methyl group to a gene (DNA methylation), which can change that gene’s expression. The B vitamins folic acid and cyanocobalamin (B12) are excellent methyl donors and have been shown to effectively contribute to gene methylation. DNA methylation can change gene expression, turning it on or off, and this can be transferred to offspring/descendents for up to four generations.

In a landmark experiment, a specific strain of mouse called agouti, which expresses a gene that results in a high probability of obesity and diabetes, was a model that yielded some amazing data. Pregnant agouti mice were divided into two groups with one group receiving a diet rich in folic acid and vitamin B12 and the other group receiving no dietary supplementation of the B vitamins. The folate and B12 methylated the agouti gene, thereby modifying its expression. This resulted in offspring of normal weight and no tendency to develop diabetes. The pregnant agouti mice that did not receive B vitamin supplementation gave birth to obese pups, many of which developed diabetes (2).

Unfortunately, a prolonged unhealthy diet and poor lifestyle choices do not “stay in Vegas” but rather are passed on to your children and their children. Of course, this applies to those in their child-bearing years. Keep in mind that not only are the children adversely affected by the parent(s) poor choice of diet and lifestyle but these parents will probably experience diminished longevity as well. And so, if you are young, be sure to make wise dietary and lifestyle choices for your future children and yourself. Older individuals also need to be prudent in their decisions on diet and lifestyle in order to extend their longevity. We all can have a longer, healthier life by using common sense and paying attention to evolving scientific information in our approach to diet and lifestyle.

Created by Dr. William J. Keller

References:

1. Bygren, L. O. et al. Acta Biotheoretica 49(1):53 (2001). Abstract available at: http://www.springerlink.com/content/x61m87x016213823/

2. Waterland, R. A. et al Mol. Cell Biol. 23(15):5293 (2003). Available at: http://mcb.asm.org/cgi/content/full/23/15/5293?view=long&pmid=12861015