Commusings: Epigenetics, Part 1

Dear Commune Community,

“I just have bad metabolism. It’s genetic. There’s nothing I can do about it.”  

I silently repeated this phrase to myself for decades as I struggled with weight. For years, I felt as if my fate was predetermined by a random combination of alleles donated by my parents. Then, I discovered epigenetics.

Across the next two Sundays, I will explore the fascinating concept of epigenetics. This term gets used in a couple of different contexts. It can refer to the study of how genes express themselves differently in relation to behavior and the environment. Epigenetics is also used to refer to the transgenerational inheritance of acquired traits.

In both contexts, epigenetics casts a shadow on our conventional understanding of genetic determinism and evolution. Epigenetics, along with the emerging fields of neuroplasticity and the microbiome, are pointing to a new understanding of the human organism not as a fixed entity with a sealed fate, but as a fluctuating process changing in relation to its exposome – the foods we eat, stress, our relationships, environmental toxins, our feeling and thoughts.

Consider this axiom uttered by Alan Watts decades prior to any discussion of the epigenome: You cannot separate the function and behavior of your organism from the function and behavior of your environment.

Here’s the empowering news: You have agency! You can the bend the arc of your health through changing your behavior and your ecosystem.

In today’s musing, I will excavate the former meaning of epigenetics: how our genes change expression in relation to environment. Next week, I will tackle transgenerational inheritance.

Here at [email protected] and evolving on IG @jeffkrasno.

In love, include me,
Jeff

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Epigenetics, Part 1

In 1953, James Watson and Francis Crick barged into the Eagle Pub in Cambridge, England and brashly proclaimed that they had discovered “the secret of life.” There was justifiable reason to enjoy a pint (or three) for Watson and Crick had unearthed the structure of DNA, the chemical that encodes instructions for the building and replication of life.

Watson and Crick proposed that the DNA molecule was made up of two chains of nucleotides paired in such a way that they form a double helix. This spiral-staircase-like structure explained how the DNA molecule could replicate itself during cell division, enabling organisms to reproduce themselves with amazing accuracy (minus the occasional mutation).

For five decades, this monumental discovery propelled biology on a quest to study and unpack the basic building blocks of life. It anchored a paradigm that envisioned life as fixed, pre-determined by a combination of nitrogen-containing base pairs, the sequence of which informs your specific genetic make-up. Biology became consumed by the idea that we could map the human genome and isolate every gene responsible for the production of every protein, every behavioral trait and even every disease. This fixation culminated in the Human Genome Project.

Launched in October 1990, The Human Genome Project was the largest collaborative international scientific research project in history. Its goal was to identify, map and sequence the entirety of the human genome.

Given the vast intellectual prowess of Homo Sapiens and the hundreds of thousands of proteins coursing through our veins, scientists justifiably presumed that this mammoth effort would likely map a robust 6-figure genome.

However, when the tally was complete in 2004, the number of protein-coding genes in human beings totaled approximately 22,300, the same range as in other mammals. We barely outscored a fruit fly, which boasts 14,000 genes and lives barely a month. Indeed, Homo Sapiens (which translates as “Wise Human”) have an equivalent quantity of protein-coding genes as a guppy.

The Human Genome Project was a triumph in international scientific cooperation and its results were integral to our understanding of human life. The mapping and sequencing of human genomics opened up possibilities for identifying genetic variants that increase the risk for common diseases.

Undoubtedly, there are variations known as single nucleotide polymorphisms (SNPs) that predispose a person to disease. For example, sickle cell disease is a genetic disorder caused by a mutation in both copies of a person's HBB gene. Mutations in the BRCA1 gene are associated with an increased risk of breast cancer. Two copies of the APOE4 allele renders a person 8 to 10 times more likely to develop late-onset Alzheimer's disease. And while the exact cause of type 1 diabetes is unknown, the risk of developing of it is increased by certain genetic variants.

All this said, the scant number of human genes raised as many questions as it answered.

How do we make hundreds of thousands of proteins from only 22,300 recipes? Why do some people with the BRCA1 mutation get cancer and others don’t? How and why do some genes “decide” to express themselves and others do not? Could significant aspects of human health be centered around non-human cells?

Similar to how Newtonian physics sought to find the universe’s smallest component parts as a means to explain the nature of reality, many biologists believed that DNA held a similar promise. However, just as Einstein found that matter consisted of patterns of energy in constant flux and relationship, and just as the Buddha posited his theory of impermanence and dependent origination in which everything changes in relation to everything else, modern systems biology points to the same satori. 

We are not fixed beings with pre-determined, hard-coded fates. We are energetic fluctuating forms, changing in relation to our environment and behavior. This new age of agency is a paradigm shift. It is both incredibly empowering – and a little scary for reasons I will soon explain. The ebb of strict genetic determinism has given way to the rising tide of the emerging fields of epigenetics: how gene expression modifies in relationship to the inputs your body receives over the course of a lifetime.

Let me explain epigenetics by analogy with my recent and first ever public piano performance. I had some pre-show jitters but I did a little box breathing back-of-house and arrived on stage without any nerves. I sat at my old, rickety, 1970s Wurlitzer piano and beheld the keys. There they were, exactly as I had left them. I ran my fingers up a chromatic scale starting on A and ending on G#. The notes never change, but I do. At times, I am relaxed and dexterous and, at other times, I am stiff and clunky.

The piano player, me in this case, is the epigenome — he or she who sits above the keys and influences their expression. My DNA is like the 88 keys on a piano. It’s the hand I’ve been dealt, warts and all. But what keys will I “turn on?” And will they produce clusters of harmonious tones or will they drive people from the club with their dissonance?

Parenthetically, the gig went great.

Yes, our DNA predisposes us to certain conditions — on occasion, definitively. But, as it pertains to chronic disease, the era of genetic determinism is withering. 90% of chronic disease is determined by our behavior and our environment.

Epigenetics, the changing expression of our genes, has now taken center stage. Our genes are expressed like a piece of music, and this expression can be health conferring or health compromising. For example, tumor suppressor genes can turn on in response to specific nutrients. Just like a well-rested, properly-fed pianist will leverage the keys at his disposal for beauty and coherence, the same is true of our bodies. 

Epi means “above.” Genetics refer to my coding – or genome. Epigenetics, then, is what exists “above my genes,” which is why sometimes I called my pinchable muffin top my “epigenome”— as this fat innertube existed “above my jeans.” 

As noted in my preamble, the term epigenetics gets used in two different, but related, ways. The primary definition of epigenetics is the study of how gene expression modifies in relationship to behavior and the environment.

Numerous lifestyle factors can impact epigenetic patterns including diet, obesity, physical activity, tobacco smoking, alcohol consumption, environmental pollutants and psychological stress. In other words, these inputs can change how your genes express.

A gene provides information. That information is used in the synthesis of an end product. Gene expression is the process by which information from a gene produces end products, such as proteins or non-coding RNA, and ultimately impacts a phenotype – or the observable traits – as the final effect.

To better understand the nature of epigenetics, let’s have a quick refresher on genetics.

You have DNA that you inherit from your biological mother and father. There are four nitrogen-containing bases that pair up to form fixed nucleotide sequences. These are adenine (A), cytosine (C), guanine (G) and thymine (T). These bases form specific pairs (A with T, and G with C). It’s the combination of these bases that creates the underlying code that determines your morphology — skin, hair and eye color among other traits.

Your DNA is wrapped in a protein called histone and organized along 23 pairs of chromosomes that exist in the nucleus of every human cell in your body (with the exception of red blood cells). These chromosomes house your genes. 

Your genes provide the recipes for producing proteins, the codes for how to sequence amino acid building blocks. We often associate protein with muscle. And, it’s true, our genes have the codes for the growth of muscular structure known as hypertrophy. But proteins wear many cloaks of identity. They can be antibodies, contractile proteins, enzymes, hormonal proteins, structural proteins, storage proteins and transport proteins. 

Here’s a way to think about it. The DNA is the master cookbook locked inside the inner sanctum of the nucleus. It contains recipes. These recipes provide the proper sequencing of amino acids, the ingredients. These recipes are messengered out of the nucleus and into the kitchen of the cytoplasm. The ribosomes are the line cooks. They receive the recipes and then make the dish. Ribosomes link amino acids together in the order specified by the codes of messenger RNA molecules to form chains of amino acids that we know as peptides and proteins. 

But what’s on the menu tonight? Well, that’s the job of the head chef, of course. He determines what recipes will make the specials menu. In this manner, the chef is the epigenome. She turns genes on and off. The chef is, in turn, influenced by many environmental factors. These ever-changing dynamics determine whether or not the restaurant (your body) is a smashing success or shutters pre-maturely.

So … how does this all work? What determines whether a gene is turned on or off?

DNA methylation is one of the most common mechanisms in epigenetics. It involves the addition of a methyl group (one carbon atom bonded to three hydrogen atoms) to the DNA molecule, usually at a cytosine nucleotide.

This molecule, which curiously resembles a lollipop, connects to a gene promoter, a region of the DNA sequence that initiates transcription of a particular gene. This tryst generally leads to repression or the "silencing" of that gene. This is because the methyl groups prevent transcription factors and other proteins required for transcription from accessing the DNA and initiating the process.

Hypermethylation, therefore, refers to the excessive methylation of certain genes. This can lead, for example, to the silencing of tumor suppressor genes, which can potentially lead to the development and progression of cancer.

For instance, the hypermethylation of promoter regions in BRCA1, a gene associated with breast and ovarian cancer risk, can silence the gene, disabling its tumor-suppressing properties and increasing the risk of cancer. 

But, again, we are not fixed. Epigenetic changes are reversible. It is possible to turn genes back on that have been silenced by hypermethylation.

What does this have to do with health and longevity?

Your chronological age is reflective of the number of orbits you’ve traveled around the sun. I was born in 1970, so, as I sit here, my chronological age is 53. Chronological age is a fixed value.

Biological age is a measure of how well a person's physiological systems are functioning compared to others of the same chronological age.

A person who is 53 years old chronologically might have a biological age of 40 because they eat a healthy diet, exercise regularly, don't smoke and manage stress. This means their body functions as well as the average 40-year-old's. What is considered “average” in the modern world is another discussion.

Biological age can be estimated in several ways, including through measures of cardiovascular fitness, telomere length and more recently through the Horvath clock that measures DNA methylation patterns.

The original Horvath clock, named after its creator Dr. Steve Horvath and published in 2013, uses the methylation status of 353 specific sites on the DNA molecule to estimate biological age. This estimate is often referred to as "epigenetic age" or "methylation age."

So why do genes get methylated?

Methylation patterns change naturally as we age. Some areas of the genome tend to become hypermethylated as we hurtle around the sun, while others may become hypomethylated. These fluctuations can influence the aging process and contribute to the development of age-related diseases.

Environmental factors can also play a significant role in DNA methylation patterns, often leading to changes in gene expression. These include:

Toxic Exposures: Certain toxins, such as heavy metals including lead, arsenic and mercury can interfere with DNA methylation processes and lead to changes in gene expression. Exposure to these can come from environmental pollution, certain occupations and certain consumer products.

Lifestyle Factors: Smoking, alcohol consumption and physical activity levels have all been linked with changes in DNA methylation patterns. Smoking specifically has been associated with hypermethylation of certain genes that could potentially contribute to the development of diseases like cancer. 

Stress and Trauma: Both physical and psychological stress can lead to changes in DNA methylation. This is part of the reason why severe or prolonged stress is often associated with poor health outcomes.

Prenatal and Early Life Exposures: The prenatal and early postnatal periods are particularly important for setting DNA methylation patterns. Factors such as maternal diet, exposure to toxins and stress levels can all influence DNA methylation in the developing fetus and may have long-term effects on health.

What Is Epi-nutrition?

In her Commune course and in her book “Younger You,” Dr. Kara Fitzgerald provides an account of a 2020 study in which she reduced biological age by three years in just eight weeks. Her team followed a group of healthy male adults who adopted specific diet and lifestyle protocols. Dr. Fitzgerald is at the forefront of the emerging field of study known as epi-nutrition, how food impacts gene expression. Dr. Kara specifically studies how nutrients affect methylation processes.

Several nutrients and foods can contribute to healthy DNA methylation. They deliver the necessary compounds (or cofactors) required for methylation or help in the production of S-adenosylmethionine (SAMe), which is the main methyl donor in the body.

Here are some key nutrients that impact methylation and the foods where they can be found:

1. Folate (Vitamin B9): Folate is a crucial nutrient that helps form the methyl groups needed for DNA methylation. Foods rich in folate include leafy green vegetables (like spinach and kale), legumes (like lentils and chickpeas), fortified cereals, and liver. 
2. Vitamin B12: Vitamin B12, or cobalamin, is also crucial for DNA methylation, as it works closely with folate in the methylation process. Foods high in vitamin B12 include animal products like meats, milk, cheese, and eggs. Some plant-based foods are also fortified with B12.
3. Vitamin B6: Vitamin B6 helps in the conversion of homocysteine to SAMe. Foods rich in vitamin B6 include fish, beef liver, potatoes and other starchy vegetables and non-citrus fruits.
4. Choline: Choline can be converted into betaine in the body, which is used in the methylation cycle. Foods high in choline include eggs, liver, salmon, chickpeas and wheat germ.
5. Methionine: Methionine is an amino acid that is used to make SAMe in the body. Foods high in methionine include meats, fish, dairy products, eggs, nuts and soybeans.
6. Betaine: Betaine can donate a methyl group to homocysteine to form methionine, which then contributes to the methylation process. Good sources of betaine include beets, spinach, quinoa and wheat bran.

There are also new studies that suggest that consuming adaptogens may also lead to healthy methylation processes.

Adaptogens are a class of plants and herbs that help the body resist different types of physical, chemical and biological stressors. They have been used in herbal medicine for centuries, particularly in Ayurvedic and traditional Chinese medicine. 

For instance, certain bioactive compounds in green tea have been found to affect DNA methylation. Specifically, the polyphenol EGCG has been found to inhibit DNA methyltransferases, enzymes that add methyl groups to DNA, potentially leading to the reactivation of silenced genes.

Another example is curcumin, the active ingredient in turmeric. Curcumin has been shown in some studies to affect DNA methylation patterns, which might contribute to its potential anticancer properties.

Some other examples of adaptogens include ashwagandha, rhodiola, ginseng and holy basil (also called tulsi).

By eating a whole foods diet (including the aforementioned nutrients), getting proper exercise, managing stress and avoiding toxicity, we are not only upgrading our metabolism, cardiovascular health and immune system, but we are also impacting our physiology at its source.

The study of epigenetics is nascent. The torch that scientists are bringing to it reveals a vast, mysterious obsidian sky – full of questions. However, the challenges to medical orthodoxy and the efflorescence of longevity science since the beginning of the 21^st century in many ways reflects the upending of Newtonian physics at the beginning of the 20^th century.

Einstein, Bohr, Planck and others pointed to a world that wasn’t fixed, that could not be reduced to its smallest component parts. At the quantum level, all of existence is a vibratory dance of energy. The emerging fields of epigenetics, neuroplasticity and the microbiome have demonstrated a similar phenomenon – one with ancient Eastern roots. The human body is not fixed but rather exists as a fluctuating process in constant interaction with its environment.

Through modifying our exposome, we can influence the expression of our genome. We can heal. We can move toward wholeness.