Written By: Kevin Cann
Many of us think that we are doomed to a life of obesity or disease because of our genes. The truth is, we may be more genetically predisposed to certain metabolic conditions or disease states, but that does not mean there are not things we can do to alter this gene expression. The idea that our genes react to environmental and internal stimuli is referred to as epigenetics. Our genetic code is wrapped up into our DNA and paired into 23 sets of chromosomes.
The DNA then wraps itself around alkaline proteins called histones. These histones then give the DNA structure. These newly formed structures are referred to as nucleosomes. On the outside of these histones are chemical messengers that listen for cues from the environment and from our internal systems. This whole structure is known as the epigenome. When the chemical messengers receive a stimuli, they will react by tightening themselves around certain genes to make them inactive so that they cannot be read by other cells. On the other hand they will relax themselves around other genes so that they are easily accessible. Our DNA we are stuck with, but our gene expression can be altered.
The elasticity of our epigenome is critical for human survival. It allows us to adapt and survive in changing environments. Diet and stress play an important role in gene expression. An interesting study just came out of UMASS Medical School and was published in the journal Cell regarding diet and gene expression. The researchers concluded their study by saying even the smallest amount of food can alter gene expression. The interesting piece is that the gene regulators that were affected by nutrition in the study also play a role in maintaining human circadian rhythm, and they react very quickly to food choices (http://www.sciencedaily.com/releases/2013/03/130328125102.htm). This is important to the individuals that are genetically predisposed to obesity or disease and/or making lifestyle choices that are causing negative gene expression. Everything in moderation is not the key. This is also important for those that may have a genetic disorder.
Altered circadian rhythm and increased oxidative stress are largely responsible for the onset of symptoms seen in Huntington’s Disease (http://robbwolf.com/2013/03/13/understanding-combating-oxidative-stress-huntingtons-disease/). This concept becomes extremely important for those that tested positive for the abnormal gene. Every wrong food choice, as well as a failure to deal with stress, can speed up the onset of symptoms. This goes for the other direction too. Every good food choice and the ability to manage stress can go a long way to prolonging positive gene expression. Maintaining an appropriate circadian rhythm is critical to overall health for the entire population. Disruption of circadian rhythm has been linked to heart disease, diabetes, obesity, thrombosis, and inflammation (http://circres.ahajournals.org/content/106/3/447.short).
Getting back to gene expression, our bodies turn off genes through a process called methylation. To keep it simple this is adding a methyl group to the DNA. As of late researchers have been looking at methylation as a primary role player in the onset of certain diseases. It is believed that methylation plays an important role in the stability of trinucleotides. In a trinucleotide repeat disorder such as Huntington’s Disease, this is important to understand. There are germinal and somatic cells within our system, and methylation is in charge of maintaining their stability.
Researchers have found that the CAG repeat in HD is due to somatic instability (http://hmg.oxfordjournals.org/content/18/16/3039.full). This leads to a theory that decreased DNA methylation may be at the center in the abnormal gene expression seen in HD. Especially when the somatic instability is correlated to the onset of symptoms. Current medications for HD are centered around silencing genes. However, we have a natural ability to do this on our own.
There are some more interesting studies that have come out of Massachusetts. This one came out of MIT. Researchers found that cells with the Huntington protein had dramatically different methylation patterns then those cells with the normal gene. Some had gained methyl groups while others had lost them (http://www.medicalnewstoday.com/articles/255191.php). An interesting note from that study is the cells with the Huntington protein attack the regions of the brain that are responsible for growth and function. This may be a reason for the quick decline in symptoms once they begin. The brain is not allowed to grow and function properly all while cells are being destroyed. However, if this was going on from birth why do symptoms not begin until later in life?
The reason may be that the methylation process changes over time from the decreased glutathione and the increased oxidative stress seen in patients with HD. Methionine, a methyl donor, becomes depleted as glutathione becomes depleted (http://www.cancerletters.info/article/S0304-3835(97)00300-5/abstract). Less glutathione equals less methionine, which leads to a decrease in methylation, which leads to less of an ability to silence the abnormal gene. The role of oxidative stress in disease does not happen over night, and does take time. Perhaps this is why the onset of symptoms occurs between 35-50, and also may explain why there is such a wide range of age of onset amongst similar diagnosis.
A common issue found in decreased methylation is a problem with methyltetrahydrofolate reductase (MTHFR) gene. The good news is this does not seem to be a problem in patients with HD (http://www.jnrbm.com/content/4/1/12). Where I stand right now is that if we monitor and maintain glutathione levels, we can limit the damage of oxidative stress while maintaining methylation levels by way of the glutathione and methionine relationship.