Epigenetics Explained

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DNA Spiral

Our outer world greatly impacts our inner world, which is where epigenetics comes into play. Epigenetics is one of the hottest fields in the life sciences; it’s a phenomenon with wide-ranging, powerful effects on many aspects of biology and enormous potential in human medicine. As such, its ability to fill in some of the ‘nature vs. nurture’ gaps in our scientific knowledge is mentioned everywhere from academic journals to the mainstream media. But what exactly is epigenetics? In this article, we’ll give you a crash course into the study of epigenetics, its importance to science, and how your lifestyle can impact both you and your family.

What Is Epigenetics?

The prefix “epi” means “above”, so the word epigenetics literally means “above genetics.” Epigenetics is the study of inheritable changes in gene expression (active versus inactive genes) that don’t involve changes to the underlying DNA sequence. These are changes to the way genes are read, not changes to the actual DNA. In short, epigenetics is the study of genes and how they can be amplified or suppressed through your habits and lifestyle.

If you’re new to epigenetics, here is a brief look at biochemistry to make epigenetics easier to understand:

  • Cells are fundamental working units of every human being. All the instructions required to direct their activities are contained within the chemical deoxyribonucleic acid, also known as DNA.
  • DNA from humans is made up of approximately 3 billion nucleotide bases. There are four fundamental types of bases that comprise DNA – adenine, cytosine, guanine, and thymine, commonly abbreviated as A, C, G, and T.
  • The sequence of the bases is what determines our life instructions.
  • Within the 3 billion bases, there are about 20,000 genes. Genes are specific sequences of bases, which provide instructions on how to make the proteins that tell cells what to do.

Epigenetics can be tricky to truly understand. Nessa Carey, in her book Epigenetics Revolution, gives an excellent analogy that breaks down the essence of epigenetics. Carey says to think of the human lifespan as a very long movie. The cells would be the actors and actresses, essential units that make up the movie. DNA, in turn, would be the script — instructions for all the participants of the movie to perform their roles. 

Subsequently, the DNA sequence would be the words on the script, and certain blocks of these words that instruct key actions or events to take place would be the genes. The concept of genetics would be like screenwriting. Epigenetics, then, would be like directing. The script can be the same, but the director can choose to eliminate or tweak certain scenes or dialogue, altering the movie for better or worse. 

A Brief History of Epigenetics

What began as broad research focused on combining genetics and developmental biology by well-respected scientists (Conrad H. Waddington and Ernst Hadorn) during the mid-twentieth century has evolved into the field we currently refer to as epigenetics. The term epigenetics, which was coined by Waddington in 1942, originally described the influence of genetic processes on development.1

During the 1990s there became a renewed interest in genetic assimilation. This led to the clarification on the molecular level of Waddington’s observations. He found that environmental stressors caused genetic assimilation of phenotypic characteristics in Drosophila fruit flies.2 For Waddington, it was unclear how the environmentally induced phenotypic change in the first generation of fruit flies had become genetically fixed. He then noted that the answer is epigenetics.

Since Waddington’s study on fruit flies, research efforts have been focused on unraveling the epigenetic mechanisms related to these types of changes.3

Waddington and Hadorn

Left, Conrad H. Waddington (Nature); Right, Ernst Hadorn (Semantic Scholar)

Types of Epigenetic Modifications

Epigenetic changes affect gene expression in different ways. Types of epigenetic changes include:

DNA Methylation

DNA methylation works by adding a chemical group to DNA. This group is added to specific places on the DNA, where it blocks the proteins that attach to DNA to read the gene, called mRNA. This chemical group can be removed through a process called demethylation. These processes can be thought of as a light switch, where methylation turns genes off and demethylation turns genes on.

Histone Modification

DNA wraps around proteins called histones. Genes can be turned up or down depending on how tightly they are wrapped around the histones. Think of it as a volume knob. DNA that is wrapped tightly around histones cannot be accessed by the mRNA in the copying process, and may not show up at all. 

If the genes are more loosely wrapped around the histones, they will be more easily read by the proteins and be more pronounced. Marks can be attached to these histones that loosen or tighten the genes around them depending on the environmental factors that affect you.

Epigenetic Inheritance

In the past, it was believed that a new embryo’s epigenome was completely erased and rebuilt from scratch, however, this isn’t completely true. Some epigenetic marks remain in place as genetic information passes from generation to generation through a process known as epigenetic inheritance.

Epigenetic inheritance is an unconventional finding; it goes against the idea that inheritance happens only through the DNA code that passes from parent to offspring. It essentially means that a parent’s experiences, in the form of epigenetic tags, can be passed down to future generations.

Most complex organisms develop from specialized reproductive cells (eggs and sperm in animals). Two reproductive cells meet, then they grow and divide to form every type of cell in the adult organism. For this process to occur, the epigenome must be erased through a process called reprogramming.

At certain times during development, specialized cellular machinery scours the genome and erases its epigenetic tags to return the cells to a genetic blank slate. Yet, for a small minority of genes, epigenetic tags make it through this process and pass unchanged from parent to offspring.

For instance, a study found that if a grandparent smoked, the grandchild will be more likely to have asthma based on epigenetic markers. The gene that produces asthma may still have the epigenetic tag that activates it.

How Epigenetics Can Change

Any outside stimulus that can be detected by the body has the potential to cause epigenetic modifications. It’s not yet clear exactly which exposures affect which epigenetic marks, nor what the mechanisms and downstream effects are, but there are several quite well-characterized examples, from chemicals to lifestyle factors to lived experiences.

To help you visualize epigenetic changes, imagine that you are an identical twin that got separated at birth. You grew up in a fairly normal household, while your twin was sent off to be raised in a circus. Your DNA is the same, but as time passed, you would both have different epigenetic codes that change the way you look, think, or act. 

Additionally, if you ate a Big Mac every day since 1992, you would likely have a greater showing of the obesity gene than your twin. If your twin was malnourished as a child, they may not be as tall as you, but they would probably be in better shape from all the unicycle riding and trapezing they’ve done in their life. 

Maybe you led a healthier lifestyle, while your twin picked up smoking. The epigenetic tags attached to your DNA would support stronger collagen, and you would likely have fewer health problems.

Epigenetic Modulation Diagram

Source: Holos Life Sciences

Epigenetic Change Factors

Development 

Epigenetic changes begin before you’re born and continue until the day you pass. All your cells have the same genes but look and act differently. As you grow and develop, epigenetic marks help determine which function a cell will have; such as whether it will become a heart cell, nerve cell, or skin cell.

Example: Your eye cells and stomach cells contain the exact same DNA, but they work differently. Epigenetic marks ensure that stomach cells create stomach acid, but the cells in your eye make sure that you can see. 

Trauma

Childhood abuse and other forms of early trauma also seem to affect DNA methylation patterns, which may help to explain the poor physical and mental health that many victims of such abuse face throughout adulthood.

Example: Childhood trauma is associated with negative health outcomes, both mentally and physically. In one study, individuals exposed to multiple types of childhood trauma showed an increased risk of early mortality, which decreased their lifespan up to 20 years.

It was also found that physically, childhood trauma is associated with increased risk of cardiovascular disease, autoimmune disease, gastrointestinal symptoms, poor dental health, obesity, and type 2 diabetes. Thus, these traumas are scientifically proven to greatly impact the modification of DNA methylation.

It stands to reason, then, that trauma experienced in one generation can become encoded into DNA and then passed on to subsequent generations, thus making history feel very present for the offspring of traumatic events. 

Lifestyle

Evidence relating to lifestyle, which includes factors such as nutrition, behavior, stress, physical activity, working habits, smoking, and alcohol consumption, has shown that environmental and lifestyle factors may influence epigenetic mechanisms, such as DNA methylation, histone acetylation, and microRNA expression.

Example: Studies have shown that smoking can potentially result in epigenetic changes. At certain parts of the aryl-hydrocarbon receptor repressor (AHRR) gene, smokers tend to have less DNA methylation than non-smokers. The difference is greater for heavy smokers and long-term smokers; however, after quitting smoking, former smokers can begin to have increased DNA methylation at this gene.

Eventually, these individuals can reach levels similar to those of non-smokers. In some cases, this can happen in under a year, but the length of time depends on how long and how much someone smoked before quitting. This also proves that epigenetics can be reversed.4,5

Epigenetics and Your Health

The last two decades have witnessed unparalleled success in identifying the genetic bases for hundreds of human disorders, and epigenetic change plays a large role. Epigenetic changes can affect your health and the health of your offspring in different ways.

Epigenetics and Disease

Your body’s health is heavily affected by your DNA. Genes passed to you from your ancestors can determine whether or not you have depression, anxiety, diabetes, glaucoma, different types of cancer, and other hereditary ailments. While you may have the genes for these illnesses, they do not always present themselves because of your epigenome. Stressors and lifestyle choices can make an epigenetic mark on your DNA that activates the genes controlling these ailments.

Example: While diabetes may run in your family, you never had a problem with it because you led a very active lifestyle. But over time, your situation changes, and you start eating less healthy foods. This can potentially trigger an epigenetic mark to attach to the gene that causes diabetes, thus activating it.

Epigenetics and Cancer

Some epigenetic marks have been known to be the cause of certain types of cancer. Different types of cancer that look alike can have different DNA methylation patterns. Epigenetics can be used to help determine which type of cancer a person has or can help to find hard to detect cancers earlier. Epigenetics alone cannot diagnose cancer, and cancers would need to be confirmed with further screening tests.6

Example: Having a mark in the BRCA1 gene that prevents it from working properly increases the likelihood of you getting breast cancer.

Epigenetics and Pregnancy

A pregnant woman’s environment and behavior during pregnancy, such as whether she eats healthy food, can change the baby’s epigenetics. Some of these changes can remain for decades and might make the child more likely to get certain diseases.

Example: During the Dutch Hunger Winter Famine (1944-1945), individuals whose mothers were pregnant with them during the famine were more likely to develop certain diseases such as heart disease, schizophrenia, and type 2 diabetes.7 Their epigenome was negatively affected due to the mother’s malnourishment, so they had a far greater likelihood of contracting illnesses later on in life than siblings who were born outside of this time period.8,9

Epigenetics Infographic

Source: Nestle

Telomeres and Aging

A telomere is a region of repetitive nucleotide sequences at each end of a chromatid. Think of a chromatid as a shoelace and a telomere as the plastic “cap” that protects the end from fraying. Telomeres are not only responsible for protecting the end of the chromosome from deterioration or from fusing with neighboring chromosomes, they, much like epigenetic modifications, are also associated with aging and age-related disease.

A young person’s telomeres are 8,000 to 10,000 nucleotides long; however, this decreases with age. Every time a cell divides, the telomere shortens, eventually reaching a critical length where they can no longer divide and will die. This attrition is compensated by telomerase activity that maintains telomere length and supports cell proliferation.

Telomerase, which is also known as the “immortality” enzyme, isn’t switched on in most adult cells; it’s only active in sperm cells, egg cells, embryo cells, and adult stem cells. Moreover, there’s a good reason telomerase is not active everywhere all the time. Recent evidence suggests telomeres also act as “molecular sensors” of genomic damage and help limit the replication of cells with highly damaged DNA.

Keeping telomeres long and enabling cells to continue dividing regardless of how much damage they’ve accumulated allows cancers to form and grow. In fact, it’s been proven that 90% of all malignant tumors have found a way to turn on telomerase and use it to essentially become immortal.

Telomeres and Aging

Source: The Wall Street Journal

A Study From Stanford University on Telomeres

Researchers at Stanford University have developed a new procedure to lengthen telomeres in chromosomes. By doing this, they’ve effectively increased the number of times cells can divide, thus turning back the clock on the cell’s aging process. 

The researchers were able to lengthen a telomere by 1,000 nucleotides, which added many years of life to the cells that underwent their process. The modified messenger RNA they used to extend the telomeres carried instructions from genes in the DNA to the cell’s protein-making factories. The RNA used in this experiment contained the coding sequence for TERT, which is the active component of telomerase. 

Most importantly, the effects of the treatment were temporary, lasting only 48 hours before the newly lengthened telomeres began to progressively shorten again with cell division. This has a multitude of benefits, which includes turning back the internal clock in these cells by the equivalent of many years of human life and increasing the number of cells available for studies. 

How To Protect And Maintain Telomere Length

Telomeres tell doctors how well your cells are aging. Ideally, your telomeres will be healthy and strong, so they can successfully fight off any mutations or degeneration in the body. While it’s normal for these telomeres to shorten during the aging process, there are a number of ways to naturally slow telomere shortening, such as:

  • Exercise: Exercise and other forms of physical activity help preserve telomere length. One large-scale investigation from the National Health and Nutrition Examination Survey (NHANES) examined over 5,000 people and concluded that individuals who exercise more tend to have longer telomeres than those who lead more sedentary lives.10
  • Eat a plant-rich diet: Individuals with healthier diets tend to have longer telomeres, a lower risk of chronic diseases, and a longer lifespan. A recent meta-analysis analyzed over 20 studies and found that a Mediterranean diet, or a plant-rich diet, was linked to longer telomeres. Unrefined grains, nuts and seeds, and coffee were also associated with longer telomeres.11
  • Keep your stress at bay: Chronic stress results in an increased secretion of cortisol that causes a rise in blood sugar and blood pressure and reduces inflammation and immune system resistance to infection. One study found that cortisol also suppresses telomerase activation in immune system cells so that telomeres are no longer protected during cell division and become progressively shorter. This can lead to early cell aging and distorted replicas of the original cell, which may result in cancer and other diseases. 12
  • Supplement with vitamin D: A strong relationship also exists between vitamin D and telomere length. A study published in The Journal of Frailty & Aging found that higher vitamin D levels were associated with longer telomere length. Vitamin D has many functions in the body, including its role in modulating inflammation — a mechanism that may protect telomeres as well.13
  • Choose folate: Folate is an essential B vitamin found in food and may play a role in protecting and increasing telomere length. Studies demonstrate that individuals with adequate folate levels have longer telomeres, while a deficiency in the vitamin can lead to DNA damage and shorter telomeres.14,15

Final Thoughts

Epigenetics, while being a fairly new field of research, has brought to light the positive and negative effects that your lifestyle has on you, your children, and even your grandchildren. We now have even more reason to live a healthier lifestyle and stop our self-destructive habits: the future of our families.

The discoveries scientists have made mean the idea that genes are “set in stone” is now obsolete. Early experiences, your parents’ and grandparents’ decisions, and the decisions you make now are all factors into the genetic pool that make you into you.

After reading the article, what parts of your life do you think you can improve upon to change your epigenome? Let us know in the comments below.

Resources:

https://pubmed.ncbi.nlm.nih.gov/22186258/ [1]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899745/#:~:text=Conrad%20H.,of%20experiments%20on%20fruit%20flies.&text=However%2C%20it%20remains%20unclear%20how,process%20of%20genetic%20assimilation%20itself. [2]

https://bitesizebio.com/8807/a-crash-course-in-epigenetics-part-1-an-intro-to-epigenetics/ [3]

https://www.raisingofamerica.org/reversing-epigenetic-effects [4]

https://pubmed.ncbi.nlm.nih.gov/30389506/ [5]

https://pubmed.ncbi.nlm.nih.gov/27895805/ [6]

https://pubmed.ncbi.nlm.nih.gov/31207580/ [7]

https://pubmed.ncbi.nlm.nih.gov/22395465/ [8]

https://pubmed.ncbi.nlm.nih.gov/29399631/ [9]

https://www.sciencedirect.com/science/article/abs/pii/S0091743517301470 [10]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855941/ [11]

https://www.stress.org/stress-aging-and-telomeres [12]

https://link.springer.com/article/10.14283/jfa.2020.33 [13]

https://academic.oup.com/jn/article/139/7/1273/4670470?login=false [14]

https://www.sciencedirect.com/science/article/pii/S0955286311000052 [15]

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