Epigenetics in Athletics Part 1: What the heck is epigenetics?

Epigenetics in Athletics- Part 1: What the heck is epigenetics?


The study of epigenetics has exploded in the last few years and the amount of new research dedicated to the field is staggering. But what exactly is it in laymen’s terms?

As you are probably aware, traditionally we all thought the sequence of the actual DNA was the be all end all. Depending on what genes you got, you were stuck with them and they defined you as a person. Once you got your sequence of genes, you were stuck with them. Although an oversimplification, people took this to mean you either had an innate trait or you didn’t.

However, epigenetics comes in and offers another piece to the puzzle. Epigenetics is the study of what goes on around the gene. We’ve discovered that it isn’t just the DNA sequence you have or whether or not you have a gene, but it’s how that gene is functioning. This is where epigenetics comes into play. It refers to processes that affect the way a gene works, or in scientific terms its expression. As most of you know, genes work by transcription and translation, which is essentially the process of copying and then translating that gene into a usable protein. Epigenetics comes into play here in that substances can come interact with the gene affecting when it’s turned on or off, the timing of the gene being turned on or off, and the amount of total protein end product that’s produced.


While It’s too complex to cover here, and frankly I don’t know enough about it to discuss the intricacies, epigenetics affect expression via several different mechanisms. One of the main ways includes substances directly attaching to the DNA and causing a switch in how that gene is working. Another way is that substances trigger constriction or loosening of the DNA itself, thus either shutting down transcription because there is no way for it to occur, or allowing for it in the loosening case.


Essentially, DNA is the hardware, while epigenetics is the software. While you’re stuck with the hardware you inherit. You can manipulate the function of the machine by changing the software.

So what’s the big deal?

It means that how the genes function can be changed based on environmental influences. Even more astounding is that these changes can be passed down to the next generation. So what you do, or what your parents did, can directly affects what happens to your kids and possibly theirs. As one of the early researchers on the subject, Dr. Pembrey, proclaimed, “You’re not what you eat. You’re what your parents ate, what your grandparents ate, and possibly what their parents ate.”

What changes?
Since the field is very new, the scientists are unraveling the mysteries behind it all the time. The central question though, is what can affect epigenetics and why does it occur?

First, let’s look at the what. The answer is a surprisingly high number of environmental stressors. While it’s beyond my knowledge scope to highlight much of the information, let’s cover some of the more pertinent findings.

The key finding is that there are many outside stressors that can change the epigenome. For instance, diet has shown to play a large role in both animals and humans. In a study that retrospectively looked at the diet and disease of a group of families in a village in Sweden, two striking findings were demonstrated. First, in males if during his childhood a man was exposed to an overabundance of food, his grandchild was more likely to die of diabetes. Similarly, on the female side, if a women was subjected to the calorie restriction of a famine when pregnant, their child was more likely have insulin resistance, and obesity among other problems.

These findings were backed up by animal studies in which, they could study changes stressors put on an animal affected gene expression in subsequent generations. In a study using rats, a low protein diet during pregnancy affected the gene expression of two different genes in subsequent generations (lillycrop et al. 2005).

But it goes beyond diet. In another study using rats, the level of care given by the mother to the baby rats after birth influenced the epigenitics of two more genes (Weaver et al. 2004). Additionally, a stress response seems to be able to make epigenetic changes. The exposure to a high level of stress hormones in the parents can lead to an abnormal production of these hormones in the subsequent generation. Additionally, it’s been shown to change cardiovascular function, body composition, metabolism, stress response, and a whole slew of other things.


While much has to be learned, it seems that there are many different stressors that cause epigenetic changes to occur.

Why does it occur?
This is all well and good, but what’s the reasoning behind epigenetic changes?

If we think of evolution or natural selection as being long term genetic adaptation to the environment, epigenetics provides for short term rapid adjustments to the environment.

In essence, epigenetics is the tweaking of the system to fit the environment.

In a review on the subject, Godfrey et al. (2007) discussed the idea of how epigenetics fits into disease. They proposed that the body makes epigenetic changes in the womb or early childhood to adapt to the anticipated environment. In other words the body is tweaking itself to make sure it’s ready for what is out there. If a mother is malnourished or lacking certain nutrients, the body makes sure to tweak the gene expression so that if a new born baby is on its way, it is prepared. For instance, you might see adaptations leading to increased fat storage, or decreased BMR as a hypothetical example. On the other hand, if a person experienced a catastrophic event that was a large stressor, then the body would make epigenetic changes to counteract this “stressful” environment. So you might get something like stress hormone suppression or fewer receptors in the next generation.

Godfrey et al. hypothesized that disease occurs when there is a mismatch between expected environment and the real environment. In their own words:

“developmental plasticity attempts to “tune” gene expression to produce a phenotype best suited to the predicted later environment . When the resulting phenotype is matched to its environment, the organism will remain healthy. When there is a mismatch, the individual’s ability to respond to environmental challenges may be inadequate and risk of disease increases.”

What that means is that if the body is expecting one environment, then gets a completely different one, disease is likely to occur because all of your adaptations were made for the other environment. An example of this from the nutrition world might be what has happened in China. Just a decade or so ago, a child coming into the world would have been influenced by his parents adaptations to a diet full of rice, fish, etc. and low in fat. Well, a few years later and that child is in an environment filled with fast food and high fat, high calorie foods with low activity levels. The childs body wasn’t adapted for that environment and there is a mismatch. While epigenetics can continually adapt, the ability to adapt decreases as you get further and further from the womb. You can still do it, it just takes longer and longer as you age. So what this means is that the greater mismatch between expected and real environment, the more likelihood for disease.

Or as they put it: “epigenetic processes tune phenotype to achieve best match to predicted environment.” And when that predicted environment differs substantially from the real environment, it’s not good news. It’s like training for a 100m sprint for years, then showing up to the Olympics and you have to run a longer race. If you had a small mismatch, it’s like running the 400m instead. Chances are you’ll be okay. But if the discrepancy between predicted and real is large, it’s like showing up and finding out you have to run the marathon.

This has large implications in disease, nutrition, and even sports performance. Since this is a sports related blog, of course that’s what I’m going to delve into:

Performance?

Up until now the focus has been on how epigenetic factors affect us negatively. Little research has been done on positive changes. But let’s take a look and see the theoretical implications.

It’s been established that in animal studies, changes can occur that affect the heart, blood flow, stress hormones, and metabolism. Granted they have been mostly negative changes, but the fact that changes can occur is intriguing. For instance, an enlarged heart has been found as a result in one study, while altered metabolism has been demonstrated in several. The intriguing thing is that change occurred at all, not that it was positive or negative.

This leads to the possibility that outside factors such as diet, exercise, stress, or any number of factors can change the expression of certain genes that enhance performance. For example, in a rat study it was found that feeding a pregnant rat B12, folic acid, and choline resulted in thin mice compared to fat mice in the control study. What happened is that these substances changed the gene expression of a specific gene, turning it off, and thus creating the thin mice (Sharp, 2008). Is it possible that what we do or what our parents did could turn on or off genes aimed at such things as mitochondria creation, or red blood cell production?

For instance research has been going on in regards to PGC-1a expression via epigenetic changes. If you recall my article on the signaling pathways for Altitude (CLICK HERE), you’d remember that PGC-1a plays a vital role in the formation of EPO, which increases our Red Blood Cells, and mitochondria. In babies, they’ve found that PGC-1a manipulation via epigenetic changes could play a role in the subsequent metabolic programming of the baby. While the link hasn’t been established, there’s potential that this could explain why smaller than average and larger than average babies tend to have lower mitochondria numbers than average sized babies (Pirola, 2009).

Additionally, recent research has asked the question if muscle fiber types are influenced by epigenetic changes. The fiber type are classified largely based on the type of Myosin Heavy Chain protein’s they have. This is where you get the classification system commonly seen that splits muscle fibers into type I, type IIa, IIx, etc. Or in the popular culture, ST, FTa, , FTx, etc.

We know that Fiber types can change. With training, you can shift slightly left or right on the fiber type continuum. With heavy damage, such as that caused by chronic stimulation in animals, the fiber types can fully change. The expression of the MHC forms in the cell tell what kind of fiber you’re going to get. What’s interesting, is that recent research has shown that epigenetic factors can manipulate this expression of the different types. In a study by Pandorf et al. (2009) they found that unloading or loading a muscle resulted in epigenetic changes that altered expression of the taking rats and suspending them so that their hind legs were unloaded (they simply used their front legs) resulted in an epigenetic change that shifted the expression of various MCH forms. What this tells us is that epigenetic factors are another regulator in what MHC is expressed. They play a role in your development of Fast Twitch or Slow Twitch muscle fibers.

All of this leads to the idea that what you do now can affect gene expression not only for yourself but also for your future children. And the question becomes can training effect the epigenome?

New research suggests so. In a study by Collins et al. (2009), they found that rats who had been exercising, had a greater epigenetic response of genes related to stress coping than control rats after being put through the stress of being thrown into cold water.

In an excellent read on the subject, Sharp elaborates on this concept, hypothesizing that training in itself leads to the stress needed to make epigenetic changes. As you may have caught on by now, there seem to be certain key periods when the body makes changes to the epigenome. While the baby is developing in the womb seems to be one, and pre-puberty being another. But what about during the rest of your lifetime?

First in scientific terms, Sharp said:
“Organisms have evolved mechanisms to influence the timing or genomic location of heritable variability
(known as ‘‘phenotypic plasticity’’). Pando and Verstrepan (2007) have shown that what they call ‘‘epigenetic switches’’ increase the variability of specific phenotypes. Also, error-prone DNA replicases
produce bursts of variability in times of cellular stress. It would appear that these mechanisms tune
the variability of a given phenotype to match the variability of the acting selective pressure – that is, an
aspect of the environment, intra- or peri-cellular (e.g.training).


Rough translation in simpler terms:
Training/cellular stress increases phenotypic plasticity. This refers to the degree that an organism can change its phenotype in response to the environment. In plain English, training increases the body’s ability to adapt to environment. The stress influences what’s changed and when it is changed. Epigentic switches try and match to the stress.

A recent study by McGee et al. (2009) seems to confirm this hypothesis. They had subjects cycle for an hour before taking muscle biopsies to look for evidence of epigenetic changes. They found that epigenetic changes were in fact taking place via a mechanism that enhances the process of transcription. This opens up the door for transcription factors like the aforementioned PGC-1a to come in and produce a result specific to the exercise stress (i.e. mitochondria creation). This would seem to lead credence to the possibility that stress, or training, increases epigenetic factors. Whether this is transgenerational (gets transmitted to the next generation) is unknown. It’s doubtful that a single workout is, but perhaps an accumulation or a very high level of cellular stress might induce transgenerational epigenetic changes.


In conclusion, training and nutrition make changes to the epigenome, essentially impacting how your genes function, not to mention your future generations. The underlying implications could be profound.

In Part 2, I’m going to look at some theoretical applications to performance, and the possible implications of epigenetics on the East African running phenomenon.


References:
Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC 2005 Dietary
protein restriction of pregnant rats induces and folic acid supplementation prevents
epigenetic modification of hepatic gene expression in the offspring. J Nutr 135:1382–
1386

Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov
S, Szyf M, Meaney MJ 2004 Epigenetic programming by maternal behavior. Nat
Neurosci 7:847–854

Epigenetic Mechanisms and the Mismatch Concept of the
Developmental Origins of Health and Disease
KEITH M. GODFREY, KAREN A. LILLYCROP, GRAHAM C. BURDGE, PETER D. GLUCKMAN, AND MARK A. HANSON


The human genome and sport, including epigenetics and
athleticogenomics: A brief look at a rapidly changing field
N. C. Craig Sharp 2008

Pirola, 2009 http://www.scitopics.com/PGC_1a_methylation_in_abnormal_weight_newborns.html
MUSCLE CELL BIOLOGY AND CELL MOTILITY
Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading
Clay E. Pandorf, Fadia Haddad, Carola Wright, Paul W. Bodell, and Kenneth M. Baldwin

3 comments:

  1. I am looking forward to part two! Great blog!

    ReplyDelete
  2. Robin5:45 AM

    Fascinating read, Steve, on many levels. Thank you~as always~for taking the time and effort to share new information with your thoughtful analysis.
    ~Robin

    ReplyDelete
  3. Great stuff, Steve. I have the feeling we are going to here much more about epigenetics and the effect this has on future generations

    ReplyDelete

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