A friend of mine recently discovered that they have a familial genetic modification that is known to increase the risk of colorectal, urinary, and uterine cancers. Unfortunately, even in this day and age, they were not aware of epigenetics and its impact on inherited disease risk. I plan on writing a post specific to limiting the risk factors for people who have this specific hereditary syndrome, but first I thought it pertinent to discuss epigenetics in general.
Epigenetics: A Definition
The technical definition of epigenetics is:
The cellular and physiological trait variations that are not caused by changes in the DNA sequence. Essentially, epigenetics is the study of external or environmental factors that turn genes on and off and affect how cells read genes.
So, while DNA (called genotype) is definitely important, what may be more important is whether or not genes are turned “on” and actually being expressed or not. The following information is a great, non-disease, example to illustrate the fact that genes themselves may be less significant than epigenetics: humans and chimpanzees share 98% of our DNA yet we are very different, why? Maybe you don’t agree that humans are all that different from chimps..then chew on this…humans and mice share 92% of our DNA.
Something else that may blow your mind is that it is possible for some epigenetic changes (epigenome) to be inherited (passed from one generation to the next). Even more awesome is the fact the sometimes even if you inherit a negative epigenome, you may be able to reverse it via your own lifestyle or if your parents health is optimal at the time of conception it can ensure proper development processes take place and delete any epigenetic changes (ie. germline reprogramming and developmental origins of health and disease)
How Do Epigenetics Work?
You may be wondering how environmental factors can affect our DNA, and honestly it is pretty complicated. However, at a high level, there are 3 basic mechanisms that lead to increased or decreased expression of or genes: DNA methylation, histone modification, and regulatory noncoding RNAs (1).
Our DNA is a kind of blueprint for our bodies but someone has to read, interpret and build from that blueprint; this is where DNA translation comes in. In order for genes to have an actual effect within the body they must be translated into proteins that carry out the action(s) the gene tells them too (keep in mind this is a very simplistic explanation). If a gene is fully translated then we can consider that gene to be expressed. Now, DNA methylation, histone modification and noncoding RNAs create a change in the structure of some aspect of the DNA translation process (1). Depending on the structural change, gene expression can either increase or decrease.
Epigenetics and Disease
While many medical conditions are linked to our DNA, what we find is that there is a limited amount of conditions that are caused 100% by our DNA. In reality, the presence of inherited genes will only increase the risk of developing certain conditions, not guarantee that an individual will develop it. Ultimately, the cause lies somewhere within the interplay of genetics, environment, and their relation to gene expression; epigenetics in other words. In the end, what matters is whether any given gene is actually turned on and expressing itself leading to physiological/physical expression of disease (phenotype).
For example, if you read my post on meditation, you will note that I provide an example of lifestyle controlling gene expression. It goes like this:
We all have specific genes that allow us to produce an inflammatory response in our body for healing and/or some event that our body perceives as stressful or threatening (negative thoughts are included here). However; meditation has been shown to reduce our bodies expression of genes leading to inflammatory responses – reference included in above link.
Obviously this shows that simple environmental factors have a large part to play in how our genes are expressed. Here are some examples of the epigenetics of specific diseases.
Allergic diseases (2):
Family history is one of the most reliable predictors of allergic diseases (asthma, dermatitis, hay fever, etc.); however, all of the genes linked to these diseases have only been shown to slightly increase one’s risk of allergic diseases. Therefore, epigenetic factors have been proposed as the most likely cause of allergic diseases. All of the following environmental factors have been linked to epigenetic changes that influence the risk of allergic diseases:
- Farm exposure during gestation and childhood
- Air pollution
- Childhood viral infection
- Developmental environment: gestational alcohol/smoking exposure, proper gestational nutrition, breast feeding.
Age-Related Cognitive Decline (3):
Significant evidence has placed epigenetic mechanisms at the core of long-term memory and learning. Not surprisingly then, what is seen with ageing is dysregulation in epigenetic mechanisms, or increased epigenetic variation…called epigenetic drift…and given the epigenetic involvement in memory and learning, we have a proposed reason to believe that this may be a key reason for age related cognitive decline and neurodegeneration.
The underlying cause of depression is not yet fully understood but there is evidence linking dysregulated gene expression (do to altered epigenetic mechanisms) as a possible cause.
Non-Alcoholic Liver Disease (5):
In animal models of genetically susceptible mice including sufficient amounts of methyl donor foods (foods high in B vitamins and choline for instance) positively impact the epigenetic mechanism called DNA methylation, and prevent the development of nonalcoholic fatty liver disease.
Rheumatic Disease (6):
Inflammatory and age related rheumatic diseases such as rheumatoid arthritis, osteoarthritis, lupus, etc. have been linked to dysregulated epigenetic mechanisms.
Dysregulated epigenetic mechanisms have also been identified as being involved in the majority, if not all type of cancers. However, to be confusing, some epigenetic mechanisms are regulated by specific genes as well as environmental factors; so, as always, the full picture is not in high definition, but we do know that environment plays a role.
A final takeaway on the epigenetics and disease front is that the cause of most diseases, even those that are strongly tied to genetics and familial history, are multifactorial and epigenetics play a key role in disease expression.
What is Considered Environment?
Clearly the key piece to epigenetics is how our environment influences the expression of our DNA. So what is considered our environment? Well, it’s pretty much everything around you: diet, exercise, social interaction, environmental toxins, stress, etc. etc. In fact, there is actually evidence that all of these factors can influence epigenetic mechanisms. Diet is heavily tied to epigenetics (8, 9) and so is environmental toxin exposure (7, 10). We all know that exercise is tied to improved health and wellness and researchers have been trying to determine exactly why this is the case for a long time, but it wasn’t until recently that it was determined that regular exercise can have a positive influence on epigenetic control (11, 12).
How to Properly Regulate Epigenetics?
In the interest of time I will keep this simple. To ensure your epigenome is functioning properly you need to give your body what it needs. At the end of the day, no matter what we talk about it always seems to break down to the same things: a whole foods, nutrient dense diet; regular exercise; stress management; and sleep.
The Barefoot Golfer