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Epigenetics - The nitty gritty changes in disease

Autoimmune diseases are damn tough to deal with and live with. When things go wrong, they go really wrong and it feels like there's no light at the end of the tunnel. However, with darkness there is always light that we can focus on, no matter how dim it may seem.

It's important not to let these diseases control you or your life, but I truly believe that for you to gain control of the disease, there are vital changes you need to make in your life. Yes, Western medicine has treatments that do wonders and manage to stop the body from attacking itself. BUT these medicines also leave the body lacking in so many ways and far too often people experience relapses whilst on these medications.

Balance is vital. Your body runs off the things that you provide it. From the food we eat to the thoughts we have, they all contribute to how our bodies function. Basically, if you put crap in, you'll get crap out, it's as simple as that. Yes, some people have genetic predispositions to certain conditions, ie runs in the family, but diseases are always multifactorial. This means that there are many different factors at play, causing diseases. So by educating ourselves on how diseases come about and what factors contribute to their development, we can control as many elements as possible, and therefore, we have a greater chance of gaining control of our health.

"Epigenetics" is the study of changes that occur in the way genes are expressed. Unlike "genetics", which studies the genetic material itself and how mutations in the genes bring about diseases/disorders or even advantageous changes, epigenetics focuses on the pathways that allow the genetic codes to be expressed as proteins, ie switching the genes on or off. If I'm losing you, hold on, here's an explanation. Think about it like this; all cells contain the same DNA right? Yes, they do! So how on earth do we have many different types of cells then? Our bodies are made up of trillions of tiny cells, all different types of cells - skin cells, nerve cells, muscle cells, cells that make up the digestive tract etc.



Our cells all start out as stem cells. Stem cells are undifferentiated cells, meaning they have no specific function or type, they are purely just a cell with the potential to become any type of cell. Through the process of epigenetics, certain genes are switched on or off and this allows the cell to become differentiated into, let's say, a skin cell. The skin cell then stays a skin cell, but the cell is continuously modified by epigenetics.

To help you understand, here is a brief explanation of how our DNA becomes the proteins that make up our bodies. (If you absolutely cannot bare science then jump to "What we eat", although I don't advise you do this because it will be difficult to fully understand what I'm talking about).

  • Our DNA is like a long string made up of two strands that wrap around each other to form a helix shape – “the double helix”. The double helix is then wound up tightly around proteins known as histones, which are like small beads that help wind up the DNA into chromatin, which is then organised into a chromosome. This is necessary so that the the DNA, which is roughly 2 inches long in one chromosome, can fit snuggly into the tiny nucleus inside each cell.

  • Every human has a total of 46 chromosomes in each cell, with the exception of the sperm and ova (eggs), which contain half the genetic material, and therefore contain 23 chromosomes. When an egg and sperm join, they make up 46 chromosomes , with half from mom and half from dad.

  • When the chromosomes are mapped out, it creates a picture known as a Karyotype. The male Karyotype has 44 chromosomes plus and X and Y sex chromosome, while the female karyotype has 44 chromosomes plus 2 X sex chromosomes. Certain conditions are associated with abnormalities in the number of chromosomes, a common example is Down Syndrome, this is when a person has 3 chromosome 21s, instead of 2.


Two strands of mirroring DNA wrap around each other to form a double helix. The helix is the wrapped around histone proteins like beads on a string. The beaded string is then fold together to make chromatin. The chromatin is organised into an X shape known as a chromosome. In the human body we have 46 chromosomes in every cell, except sperm and ova (eggs) which contain half the chromosomes, ie 23.

The normal chromosomes found in males (left) and females (right). Males are said to have a 44(XY) karyotype, meaning they have 44 chromosome pairs and an X sex chromosome plus a Y sex chromosome. Females have a 44(XX) karyotype, meaning they have 44 chromosome pairs and two X sex chromosomes. The sex chromosomes determine the physical gender of a person - XY is male and XX is female..


  • Imagine our DNA works as a zipper, the two sides mirror each other. There are 4 bases/nucleotides that make up our genetic codes. A, T, C, G. These nucleotide bases work in pairs, A pairs with T and C pairs with G. So if the one side of the zipper reads ATTCGTAG then the other side will read TAAGCATC.

  • The DNA is then ‘zipped up’ again by the ‘zipping protein’ and the newly created RNA strand moves away and is proof read to screen for errors by a ‘screening protein’.

  • When the body wants to make a protein, the DNA begins to loosen up and unravel from the histones to allow the cells DNA synthesising proteins to access the genetic codes. An ‘unzipping protein’ finds the correct part of the DNA that codes for the wanted protein, it ‘unzips’ the DNA code for that specific protein and a ‘scanner protein’ scans that code and creates or transcribes a new strand of the genetic code with the base pairs that are in the cell's nucleus (RNAs), however, the T nucleotide base is replace with a U nucleotide on the new mRNA strand (messenger RNA).

  • The DNA is then ‘zipped up’ again by the ‘zipping protein’ and the newly created mRNA strand moves away and is proof read to screen for errors by a ‘screening protein’.

  • It then moves to a ‘reader protein’, which reads the mRNA strand and creates a string of amino acids, coded for by the base pair sequence. The string of amino acids is then folded up by a ‘folding protein’ thus a protein is created.


The Helix is unzipped to expose the genetic code. RNAs found in the nucleus are then linked together to make a mirror image of the code that is needed.

The mRNA strand then leaves the nucleus and enters the cytoplasm where it will be translated into a protein. The mRNA strand moves through a Ribosome protein. As it attaches, a tRNA, which has 3 nucleotide pairs that match the code on the mRNA strand, enters that Ribosome and pairs with the correct code. When this pairing takes place, an amino acid that was attached to the tRNA is released onto the Ribosome, and begins to form a chain. A chain of amino acids make a protein. Once the code has been read and all of the amino acids are joined, the protein detaches from the ribosome, is folded correctly and thus a protein is made.

There are 3 important types of epigenetic changes.


1. The process of methylation.

This is the process in which a methyl group (usually CH3) is added to or tagged onto one of the DNA bases, usually he C base. The DNA code remains unchanged but the methyl group will cause the code for that specific gene to be switched off. Ie when the ‘scanner protein’ reads the methylated base, it knows not to transcribe the code or create a protein from that gene. If the gene is switched off, the protein it codes for will not be made.


A cytosine nucleotide base is methylated by the addition of CH2 to the Hydrogen atom (H), converting the Hydrogen atom to CH3. When read, this gene will be silenced or switched off during protein synthesis.


2. Histone modification.

Remember that histones are the beads that the strand of DNA wraps around to wind the DNA up tightly so that it can fit inside the cell. Imagine that these histones keep turning the DNA strand around themselves making the DNA wrap tighter and tighter forming ‘heterochromatin’. This would make it impossible for the DNA synthesising proteins to read the DNA sequence/ code and therefore no proteins could be created. The opposite is also true, if the histones allow the DNA to become loosely wrapped around them, then the DNA synthesising proteins can easily access the DNA sequence/ code, and proteins can be made easily.


Euchromatin is chromatin loosely wrapped around histone proteins to allow for easy access to the DNA during protein synthesis and DNA replication. Heterochromatin is when the chromatin is wrapped tightly around the histones making it difficult to expose the DNA code, therefore inhibiting protein synthesis and DNA replication.


3. Non-coding RNAs.

These are RNA stands made of varying numbers of nucleotide bases, however, these strands don’t get transcribed into proteins. These strands have the ability to greatly affect the DNA synthesis process. They play a large role in the formation of heterochromatin (tightly wrapped and unreadable DNA), in initiating methylation and histone modification, as well as having the ability to silence genes. They also play a large role in the differentiation and development of immune cells. The non-coding RNAs are extremely important in epigenetics and are key players in multiple diseases such as autoimmune diseases, cancer, metabolic disease and inflammatory processes.


The different types of non-codin RNA (ncRNA) and their different functions.

Scientists believe that it may be possible to inherit epigenetic changes that are present in the sperm or egg from our parents, this means is that what we eat or do during pregnancy, could ultimately affect our babies. However, this is still currently being studied and more information is needed before bold statements can be made. It is more common that the actual DNA we receive from our parents, contains the mutation in the DNA sequence which codes for the disease, rather than an epigenetic change. The major focus, with regards to Epigenetics, is on how environmental and lifestyle factors influence our genes and how they are expressed. And this is where my interests lie.


As I’m sure you have realised, the body is an exceptionally complicated and intricate system from the microscopic level to the visible level. So how does this all relate to Autoimmunity? Well, epigenetics and autoimmunity have a very important association. Autoimmunity occurs when the cells of the immune system lose their ability to recognise the cells of the body as ‘self cells’, they see the cells of the body as invaders and threats. How do these cells lose this ability? Surprise surprise, through epigenetics.


For goodness sakes Cayla, get to the point.


Right, so after that lengthy but vital explanation I can finally get to explaining how, what you eat and how you treat your body can cause diseases.


What we eat:

  • Food has an undeniable link to epigenetics and diseases. There are certain foods that are beneficial to us.

  • Polyunsaturated fats found in seeds, nuts, fish and oysters, are fats that have the ability to supress tumourigenic process (the formation of tumours) by reducing inflammation as a result of switching off certain parts of the inflammatory pathways.

  • Fruits and vegetables are essential for protection against disease. A single serving of Broccoli sprouts has been shown to inhibit histone modification in cells within 3-6 hours after eating them.

  • Polyphenols are natural compounds that are found in plant foods. They have the ability to reverse negative epigenetic changes that result is cancer formation. They were also shown to reduce stress and depression by modulating inflammatory processes.

  • Green tea contains a compound known as EGCG, which has been show in studies to inhibit methylation and therefore reactivate protective genes that have been silenced, through methylation, in cancer cells.

  • Curcumin, found in turmeric, is a potent anti-inflammatory, anti-cancer, antioxidant substance. I’ve mentioned this in a few of my posts as it is one of the top new substances being studied and used currently. It works in a similar way to EGCG by reversing methylation that results in inflammation and by switching off certain inflammatory pathways.


Exercise and weight

  • Most of us are aware that diets high in processed food, saturated fats and sugar can lead to weight gain and diseases such as diabetes, heart disease, cancer and autoimmune disease. A frightening fact that has come to light in recent studies shows that these food groups may have the ability to epigenetically modulate genes that could result in people becoming obese. ie these foods can trigger changes in the way the gene that affect the way your body breaks down, uses and stores energy, are expressed. That’s right folks, what you eat has the ability to trigger your body to become obese.

  • Studies show that exercise has a positive impact on methylation, histone modification and non-coding RNAs. Exercise causes increased methylation of inflammatory pathways, decreasing the amount of harmful inflammation.

  • Through the positive effects on non-coding RNAs, exercise is able to slow down the aging process by preventing shortening of telomeres. Telomeres are found at the end of chromosomes, they prevent cell damage and shortening of the DNA that occurs when cells divide. When telomeres shorten, it is noted that the aging process is accelerated.

  • Exercise also results in a positive increase of the methylation of certain lymphocytes that cause inflammation. This results in lower levels of the inflammatory lymphocytes and therefore less inflammation.

  • Exercise can switch on genes in muscle responsible for repair and growth of muscle cells.

  • · Studies show that exercise has the ability to reduce the number of non-coding RNAs resulting in a generalised reduction in diseases.


Cigarettes and Alcohol:

  • Tobacco contains multiple chemicals that are carcinogenic (cancer causing) and pro-inflammatory. These chemicals have the ability to switch off genes that code for many proteins that are responsible for preventing cancer formation and inflammation (tumour suppressor genes). When these genes are switched off, the cell loses its ability to screen for ‘mistakes’ made during cell division and thus mutations occur and cancer or other diseases are created.

  • Cigarette smoke is able to down-regulate or decrease the number of good non-coding RNA, which are responsible for healthy growth and development.

  • Alcohol has the ability to silence genes responsible for the growth and development of nerve cells found in the brain and throughout the body. It has also been linked to the development of gastric and colorectal cancers by down regulating tumour suppressor genes.

  • The reason women are not meant to drink or smoke during pregnancy is because these substances have the ability to epigenetically change the developing cells and result in harmful changes to the way the genes are expressed. Thus causing severe physical defects.


Environmental Pollutants:

  • Arsenic has the ability to cause increased methylation of tumour suppressor genes and therefore, cancer causing mutations in the DNA go unseen. Thus cancer cells are formed.

  • Benzene is an organic chemical that is found naturally in forest fires and volcanos. It is a substance used in many products we use today including; gasoline, lubricants, pesticides, dyes, rubber, plastic, lotions, synthetic fibres and more. Benzene has been linked to increased risk of all types of leukaemias and lymphomas through increased methylation of tumour suppressor genes and decreased methylation of other carcinogenic processes.

  • Air pollution is a huge issue we face currently. Ambient particulate matter (APM) is the mixture of particles that are suspended in the air. It is made up of dust, pollen, soot, smoke, industrial and agricultural by-products and products derived from burning fossil fuels. APM has been linked to multiple health issues, including heart and lung disease as well as lung cancer. These compounds epigenetically modify multiple genes resulting in methylation of multiple tumour suppressor genes as well as multiple other pathways such as oxidative stress with free radical formations and inflammation that result in heart and lung disease.


Psychological stress:

  • The current social circumstances we live in creates a highly stressed environment, fuelled on lack of sleep, working excruciatingly long with little time off and little pay. We run off stress and it is killing us.

  • Studies have shown that stress plays a role in epigenetic pathways and traumatic events in early childhood as well as later in life cause increased methylation of the receptor that binds to the stress hormone - cortisol. Thus making the body less able to deal with the increased levels of stress.

  • Studies have proven that stress-associated epigenetic changes are linked to depression.

  • The stress-associated methylation has been shown to affect genes that play a role in brain development and plasticity as well as cortisol sensitivity. Therefore, chronic fatigue, anxiety and cognitive impairment have also been linked.

  • Shift working has also been linked to epigenetic changes in the circadian rhythm (the control centre that regulates being awake and asleep). This results in higher levels of inflammation and increased levels of stress hormone, and so the stressed, sleep deprived cycle continues.

There are many other examples of compounds that cause epigenetic changes, from parabens found in deodorant, to Diethanolamine (DEA) found in make up, there are thousands of these chemicals found in the products we put on our bodies everyday. Now I know how difficult it is to avoid these completely, I have been trying to, but click on this link to read up on some of the carcinogens found in our everyday products, make yourself aware of them and do your best to avoid them if you can. https://www.healthline.com/health/carcinogenic-ingredients-your-personal-care-products


What I am trying to explain in this post is that it’s not as simple as you get diagnosed with a disease and a tablet will fix it. There are so many different factors that contribute to the disease process, and if we are aware of these factors, we can gain control of them. When we can control our exposure to good or bad factors, we can, to a certain degree, control our health. This is why it is so important to view a person in their entirety, when looking at disease. One single factor in isolation, does not cause a disease, just as one single factor in isolation, cannot cure a disease.


It is highly unlikely that the pill given to you by your doctor, or the diet someone suggested, or the essential oils and supplements recommended will cure you if you just pick one of them. However, if you combine all of these different modalities together and incorporate aspects of each of them into your protocol, you are way more likely to heal. Combining all of these elements will allow epigenetic changes to take place, these changes could help heal you.


I know this is A LOT to absorb and it is a very complex topic that I understand because of my Science and Medical degrees, so I have tried to make it easy for you to understand. I have added some references below to help guide you if you are interested in furthering your knowledge with this topic, ie go Google them! Or if you have any questions, don't hesitate to reach out and ask me.


I hope this information gave you some insight into how our bodies work and how diseases can come about, most importantly, I hope it has helped you realise that if you have a well rounded, multifaceted approach to your disease, you are more likely to gain control of it.


Sending love,


Cayla


KEYWORDS:

Epigenetics: the study of changes in an organism that come about through changes in gene expression.

Gene expression: The process in which the DNA is transformed from the genetic code into something we can physically see (ie the phenotype).

DNA Transcription: The process in which the DNA code is copied as a mirror image into mRNA.

DNA Translation: The process in which the mRNA strand is transcribe or made into a protein.

Protein Synthesis: The formation of proteins from the DNA code, through transcription and translation.

Karyotype: The visual representation of the numbers of chromosomes found within the nucleus of the cell.




Reference:

https://www.livescience.com/37703-epigenetics.html

https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0632-2

https://www.whatisepigenetics.com/non-coding-rna/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752894/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197720/

https://en.m.wikipedia.org/wiki/Epigenetics_of_physical_exercise

https://www.greenfacts.org/en/particulate-matter-pm/level-2/02-health-effects.htm#1

https://www.ncbi.nlm.nih.gov/pubmed/31005627


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