EpigeneticsHealthLongevityPerformanceThe Daily Grist

Methylation Basics

“Aging is inevitable but growing old is a choice.”
Joseph Rain
__________________

Life begins and ends at the cellular level.

The keys to your mansion of unparalleled health, performance, and longevity represent an inside-out proposition. Synergy is the lynchpin.

Compromised cellular, tissue, and organ integrity represent accelerated aging which contributes to the onset of a multitude of chronic and degenerative diseases. Accelerated aging directly incites cancer, diabetes, cardiovascular, and neurodegenerative disease risk factors.

One must understand the biological processes of accelerated aging versus wondering or merely watching it happen. The nine molecular markers of why we age are termed The Hallmarks of Aging:

→ Genomic instability;
→ Telomere attrition;
→ Cellular senescence | immunosenescence;
→ Altered intercellular communication;
→ Mitochondrial dysfunction;
→ Loss of proteostasis;
→ De-regulated nutrient-sensing;
→ Stem cell exhaustion;
→ Epigenetic alterations


Absolution

Your genetic blueprint is one of the many pieces of the complex human system. Your genetic blueprint consists of a combination of DNA markers [Adenosine – A, Cytosine – C, Guanine – G, and Thymine – T]  known as Single Nucleotide Polymorphisms [SNPs – pronounced  “snips”].                                    

SNPs represent the keys to this cutting-edge paradigm to optimize gene expression. In an ideal world the A allele pairs with the T allele and the C allele with the G allele.

Epigenetics explains gene expression through environmental stressors. Epigenetics represents the study of changes in an organism by modifying gene expression without altering the genetic code [DNA blueprint/sequence].

“Epi” is the Greek lexicon for “above.” Epigenetic markers position above your DNA sequence and impact gene expression/suppression based on lifestyle factors [methylation].

Proper gene expression is a big deal. The mayhem begins when gene expression results in suppression – and vice versa. Its impact reaches far beyond a sub-par outing at work, the gym, or the trails.

It invites inflammation, chronic and degenerative diseases, accelerated biological aging, senescence, and numerous other undesirable outcomes – no matter one’s fitness level.

The promise of epigenetic testing is its depiction of cellular integrity. When variants highlight abnormal cellular function, it allows the opportunity to reverse chronic, degenerative, autoimmune states, cancer, and accelerated biological age while improving your health, performance, and longevity via modifications to gene expression.

Epigenetic testing can reveal propensities to disease leading some people to take preventive measures. Your ability to do that depends on the predisposition and how to mitigate or prevent it. Epigenetic testing provides intelligent, data-driven, evidence-based measures and strategic actions to optimize health, performance, and longevity.

Life is not ideal and offers a different set of parameters – many unpredictable. Therein lies the benefit of matching desired outcomes with propensities.

The invaluable art of applying complicated data to complex thinking is “augmented intelligence.”  The precise interpretation of the data is the key to transcending health, performance, and longevity in life and sport. 

Your DNA blueprint is absolute – it cannot be altered. Epigenetics represents what is possible. It represents propensities versus absolutes. Think of epigenetic markers as apostrophes sprinkled above the letters of words in a sentence or paragraph [your DNA sequence].

Epigenetics represents all inputs from life. Your DNA provides instructions for proteins produced inside the cells. Epigenetic markers impact [like a dimmer switch] how genes read cells.

The beauty is that propensities can be modified to optimize health, performance, and longevity. Find below a few vital areas:

→ Sleep;
→ Stress;
→ Nutrition [nutrigenetics and nutrigenomics];
→ Supplementation;
→ Recovery;
→ Cognition;
→ Hormones;
→ Microbiome;
→ Neurotransmitters;
→ Glutathione system;
→ Nitric oxide production:
→ Plant sterols;
→ Insulin resistance;
→ Mitochondrial biogenesis; and
→ Numerous other categories


The Basics

Methylation is one of the most important processes in the body and plays a crucial part in epigenetics. Histones are a type of protein found in chromosomes. Histones bind to DNA, help give chromosomes their shape, and help control the activity of genes.

DNA methylation is an epigenetic mechanism that occurs when a methyl group [CH3] is added to specific regions of the DNA nucleotide and modifies the function of the gene expression. CH3 is one carbon atom plus three hydrogen molecules.

Methylation is a chemical modification of DNA and other molecules that may be retained as cells divide and proliferate. Methylation can alter gene expression. Chemical tags called methyl groups attach to a particular location within DNA where gene expression and regulation of the production of gene-encoded proteins occurs.

DNA methylation is a prime example of the plethora of epigenetic mechanisms:

→ Improved brain function;
→ Detoxification;
→ Energy production;
→ Converting B vitamins to active forms;
→ Flushes histamines;
→ Tissue growth;
→ Neurotransmitter production;
→ Fat metabolism;
→ And more

MTHFR [Methylenetetrahydrofolate reductase] is an enzyme catalyzing methylation at a rate more than one billion times per second. Impaired methylation due to a genetic propensity can manifest symptoms related to “The Hallmarks of Aging.” 

→ Anxiety;
→ Depression;
→ Infertility;
→ Chronic fatigue;
→ Microbiome issues;
→ Poor sleep quality;
→ Sub-par performance;
→ Histamine intolerance;
→ And more

Methylation is influenced by lifestyle choices and environmental stressors – which directly interact with your genome. Methylation is a vital tool your body implements to change, adapt, and grow – which has no endpoint. The amino acid glycine buffers excess methyl groups and maintains balance in bodily processes no matter the stressor.

Find below a few factors known to impact methylation patterns:

→ Sleep;
→ Diet;
→ Exercise;
→ Supplementation;
→ Medications;
→ Acute | chronic stress;
→ Alcohol;
→ Smoking;
→ Heavy metals;
→ Airborne pollutants;
→ Altitude;
→ Many more

The key is balanced methylation.

Two molecular beneficiaries of methylation are creatine and phosphatidylcholine.

The benefits of the former are well documented – especially in the realm of muscular strength, power, and performance. Creatine benefits your skin, hair, bones, cognition, recovery, and microbiome.

Phosphatidylcholine is vital to the digestion, absorption, and assimilation of nutrients. It flushes fat from your liver and assists as a neurotransmitter.


Terminology

Chromatin → Chromatin refers to a mixture of DNA and proteins that form the chromosomes found in the cells of humans and other higher organisms. Proteins [histones] package DNA in a genome into a highly compact form that can fit in the cell nucleus.

Chromosome → Thread-like structures inside the nucleus composed of tightly coiled DNA. Humans have 23 pairs of chromosomes.

Demethylation → the chemical process of removing a methyl group from a molecule. Demethylation replaces a methyl group with a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms. The counterpart of demethylation is methylation. DNA methylation often inhibits the expression of certain genes. This can alter how your body functions and insidiously affect your health, performance, and longevity.

Histone → A histone is a protein that provides structural support for a chromosome. Each chromosome contains a long molecule of DNA which must fit into the cell nucleus. The DNA coils histone complexes which give the chromosome a more compact shape. Histones also play a role in the regulation of gene expression.

Histones can be modified by chemical groups [methyl or acetyl] in the form of gene expression or suppression. The chemical groups regulate how tightly the DNA is coiled around histones and impact gene expression. Think of a spool of thread.

Methylation → Methyl groups attach to your DNA and modify gene expression by changing what areas of your DNA can be transcribed.

Methylation changes to DNA translate to every function in your body because these functions rely on DNA transcription.

Coding Region → Dictates the amino acid sequence of the protein encoded by the gene.

Promoter Region → Base-pair sequence of DNA to which proteins bind to catalyze transcription. 

Terminator Region → The sequence that ends the transcription process.

Transcription initiates at the “promoter region,” proceeds through the “coding region,” and finalizes its journey at the “terminator region.”

Methylation and acetylation represent critical processes in the body related to epigenetics.

Methylation silences gene expression; acetylation activates gene expression. When methylation is out of balance it causes systemic effects that can lead to undesirable outcomes. 

Acetylation is crucial to desirable outcomes. Acetylation plays a significant role in detoxification.  It works to help detoxify histamines, tobacco smoke, exhaust fumes, nutrition toxicity, supplementation overload, sleep deprivation, and medications.

Proper acetylation contributes to optimal organ functions, and shields long-term imbalances. Acetylation ignites gene expression.


Epigenetic Modification Types

DNA Methylation: refers to a chemical reaction in the body in which a small molecule called a methyl group gets added to DNA, proteins, or other molecules. Methyl groups can affect how molecules behave in the body.

The methyl groups target specific DNA locations and block the ability to “read” the gene. When this chemical group is removed the process is termed demethylation. Methylation turns genes “off” and demethylation turns genes “on.”

Histone modification: DNA wraps around histones [proteins]. If the histones are coiled tightly around the DNA they cannot be accessed by proteins that “read” the gene. The genes wrapped around histones are turned “off” and the genes not wrapped around histones are turned “on.”

Chemical groups can be added or removed from histones changing whether a gene is unwrapped [on] or wrapped [off]. Again – envision a spool of thread.

Non-coding RNA: DNA directs for making coding and non-coding RNA. Coding RNA is used to make proteins. Non-coding RNA helps control gene expression by attaching to coding RNA and certain proteins to break down the coding RNA to thwart protein production.

Non-coding RNA may recruit proteins to modify histones to impact the expression or suppression of genes.

Methylation primarily occurs at the CpG dinucleotide. CpG islands are regions with high frequencies of CpG sites. CpG islands are regions with extensive concentrations of phosphate-linked cytosine-guanine pairs located in gene promoter regions. 

DNA methylation is essentially the inactivation of gene transcription. When a methyl group is placed on a particular gene it typically gets turned off. This occurs especially at the CPG islands [the DNA sections where cytosine and guanine pairs repeat].

If genes are being expressed, these CpG sites are demethylated. and when methylated, can inactivate gene expression. Methylation is an inactive DNA mark that silences gene expression through repressive chromatin structure.

DNA in each cell is tagged with chemical groups that act as guideposts to help the cell express or suppress a gene. When the tags are correctly positioned genes are expressed properly in healthy cells.

Incorrect DNA tagging occurs when excess healthy methyl chemical groups on the cellular  DNA cause erratic gene expression or suppression.

This disrupts the continuity of information in the cell. These flags can turn off key defensive genes that help protect the cell from becoming cancerous and disrupt other processes. This is called the “CpG Island Methylation Phenotype [CIMP].”

Balanced DNA methylation is important – find below a few reasons:

→ Critical in gene expression;
→ It is the foundation for chromatin structure;
→ Modifies activation or repression transcription factors;
→ Poor methylation linked to chronic and degenerative diseases;
→ Impacts mood and behavior;
→ Mobilizes fats and cholesterol for repair or removal;
→ Regulates hormones;
→ Facilitates protein synthesis;
→ Important mechanism in memory formation and storage

Overmethylation:

→ Paranoia,
→ Self-mutilation;
→ Depression;
→ Artistic abilities;
→ Upper body pain;
→ High pain threshold;
→ Excess body hair;
→ Difficulty shutting off the mind;
→ Food/chemical sensitivities;
→ Sleep disorder;
→ Anxiety;
→ Panic tendencies;
→ Adverse reactions to antihistamines

Undermethylation:

→ Obsessive-compulsive tendencies;
→ Perfectionism;
→ High accomplishment;
→ Ritualistic behaviors;
→ Low tolerance for pain;
→ Addictive tendencies;
→ Celf-motivation;
→ Competitiveness;
→ Social isolation;
→ Plender body composition;
→ phobias;
→ Seasonal allergies;
→ Frequent headaches;
→ Boldness


WHY THIS MATTERS

When methylation is out of balance it causes systemic effects that can lead to undesirable outcomes.  There are many variables to consider such as micronutrient levels and lifestyle factors.

Optimal methylation has a significant, positive impact on numerous biochemical reactions in the body that regulate the activity of the cardiovascular, neurological, reproductive, and detoxification systems, including:

→ DNA production;
→ Neurotransmitter production;
→ Detoxification;
→ Histamine metabolism;
→ Estrogen metabolism;
→ Eye health;
→ Fat metabolism;
→ Cellular energy;
→ Liver health

SAMe – The Universal Donor

The complex human system mandates synergy to optimize health, performance, and longevity in life and sport. 

A universal methyl donor – SAMe (S-adenosylmethionine) – transfers CH3 to and from bioactive compounds [proteins, enzymes, hormones…] in your body. The compounds must be methylated to function properly and create the required substances for your body.

This is a big deal. Optimal health mandates a methylation/demethylation balance. Gene expression or suppression is powerful. Each can influence health aspects such as disease risk, neurological disorders, cancer, and other manifestations.

CH3 converts the amino acid methionine to SAMe which donates methyl groups as it travels the body to bolster metabolism. SAMe converts to the amino acid homocysteine in your blood to rev the glutathione system – the master antioxidant system of your body.

SAMe is recycled to methionine to repeat the process. The mayhem begins when there is a shortfall of critical nutrients [methyl B12 and methyl folate – 5-MTHF] which incurs homocysteine accumulation within your body. Elevated homocysteine levels represent risk factors for oxidative stress:

→ Clotting;
→ CV disease;
→ Parkinson’s disease;
→ Asthma;
→ Cognitive decline;
→ Microvascular damage;
→ ADHD;
→ Stroke;
→ Heart attacks;
→ And more

SAMe provides its methyl groups throughout the body in the spirit of optimal cardiovascular, neurological, reproductive, and detoxification systems. 

Folic acid from the diet or supplements must be converted to its active form [5-MTHF] before it can be used in the body in the methylation cycle. Data shows about 60% of the United States population has a genetic propensity that makes the production of 5-MTHF a challenge.

A deficit in SAMe production results in the following molecular mischief:

→ Glutathione;
→ Coenzyme Q10;
→ Melatonin;
→ Serotonin;
→ Nitric oxide;
→ Norepinephrine;
→ Epinephrine;
→ L-carnitine;
→ Cysteine;
→ Taurine

Epigenetic testing can reveal propensities to disease leading some people to take preventive measures. Your ability to do that depends on the predisposition and how to mitigate or prevent it.

Epigenetic testing provides intelligent, data-driven, evidence-based measures and strategic actions to optimize health, performance, and longevity.

Key foods and nutrients to optimize methylation include:

→ Asparagus;
→ Avocados;
→ Broccoli;
→ Brussels sprouts;
→ Green, leafy vegetables;
→ Legumes [peas, beans, lentils];
→ Ancient grains [quinoa, amaranth];

→ 5- MTHF [active folate];
→ Methionine;
→ Homocysteine;
→ Thiamin Diphosphate [active B1];
→ Riboflavin 5’ – Phosphate [active B2];
→ Nicotinamide [active B3];
→ Pyridoxal 5’ – Phosphate [active B6];
→ L-methyl folate [active B9];
→ Methylcobalamin [active B12];
→ Betaine [Trimethylglycine];
→ Vitamins D3 + K2;
→ Iron;
→ Phosphorus;
→ Sulfur;
→ Magnesium;
→ Potassium;
→ Zinc

Lifestyle changes include:

→ Engaging in regular physical exercise;
→ Avoid excessive alcohol consumption;
→ Quitting smoking;
→ Avoid excessive coffee consumption [no more than five cups daily].


Proper methylation is vital to health, performance, and longevity. Because it influences so many systems in our bodies explains why it is often overlooked – which can severely impact how your body functions. Connect with your healthcare practitioner if you have concerns about your CH3 cycle.

Aging is inevitable. Growing old is not. The aging process is accompanied by decreased organ function and increased disease incidence, limits human lifespan, and has attracted investigators for thousands of years.

In recent decades, with the rapid development of biology, scientists have shown that epigenetic modifications, especially DNA methylation, are key regulators involved in this process.

Recent research efforts provided compelling evidence of genome-wide DNA methylation alterations in aging and age-related disease. It is currently well established that DNA methylation biomarkers can determine the biological age of any tissue across the entire human lifespan, even during development.

Evidence suggests that epigenetic age acceleration is strongly linked to common diseases or occurs in response to various environmental factors. DNA methylation-based clocks are proposed as biomarkers of early disease risk predictors of life expectancy and mortality.

Longevity can be regarded as a manifestation of healthy aging. In contrast, accelerated aging is always accompanied by the onset of chronic diseases, particularly degenerative diseases, which ultimately result in disability or premature death.

Some researchers consider age-related degenerative diseases as one of the factors that accelerate the aging process

Researchers have focused on studying the long-term effects of environmental stress on gene expression regulation. Epigenetic modifications are proposed to play a crucial role in the progression of aging.

We have the technology to eliminate the guesswork, decode superhuman, and propel your limitless potential. Epigenetics represents an unprecedented, bold, medical paradigm leveraging cutting-edge technology to shift genetic expression with mind-blowing results in life and sport.

Click Performance Medicine to learn how to transcend your health, performance, and longevity in life and sport.

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Jeff Kildahl

Jeff Kildahl is a writer, author, researcher, and publisher leveraging technology to transcend health, performance, and longevity. Performance Medicine™ is a visionary consulting firm providing ultra-endurance athletes with synergistic solutions to master the difference between effort and struggle. He merges the highly-specialized modalities of glycocalyx testing, blood analysis, biological age assessments, HRV testing, and comprehensive epigenetic evaluations with tailored guidance to optimize health, performance, and longevity in life and sport. Kildahl is credentialed in bioenergetics, biomechanics, metabolic efficiency™, sports nutrition, epigenetics, and natural medicine. He is a dynamic member of CUBE™ ~ a professional speakers group ~ empowering others to harmonize the "Keys to Living in the Song of Life." He is a sponsored vegan ultra-endurance athlete and philanthropist. His company sponsors the spirited initiatives and global events of the United States Snowshoe Association, the World Snowshoe Federation, the American Trail Running Association, the United States Trail Running Conference, and other innovative ventures. He is the publisher of SYNERGY™ | Performance Medicine™ Magazine - a cutting-edge publication designed to impart the innovative principles of Performance Medicine™. Kildahl is the creator and president of Performance Medicine™ → https://pmsynergy.com.

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