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Methylation, in many ways, is a type of molecular language or instruction per se; it indirectly impacts cellular communication. It’s key for normal development. It helps regulate various functions in the body. And it even has the power to turn genes on and off.

It’s likely you’ve come across the term “methylation” on popular health and wellness podcasts or social channels—or perhaps through research driven by your own curiosity. Yet, this technical-sounding term can be confusing (to say the least). Frequently talked about in relation to ageing and longevity, there’s so much more to methylation than its potential in the anti-ageing realm.

While methylation is invisible to the naked eye, its significance behind the scenes should never be underestimated. So, what does methylation mean when it comes to your health and wellness? How does it impact biological processes in the body? And most importantly, what can you do to enhance this beneficial process? Read on to discover the basics of methylation and more.

The Importance of Methylation in Biological Processes

First, what is methylation exactly? Put simply, methylation is a chemical process in which a tiny “methyl” group (CH3) is added to a molecule, like DNA, RNA, or proteins. This additional methyl group can affect how genes are used or how specific cellular processes work. 

Think of it this way: The methyl group added is like a small tag attached to the molecule that tells the cell what to do with it as shown in the image below —such as activate or deactivate certain genes or control specific cell functions. 

Role of DNA methylation in Disease | labclinics.com

This can further guide cellular development (particularly in relation to the development that occurs early on in life), whether or not specific diseases arise, and whether or not certain genes are expressed. Methylation also plays an invaluable role in DNA repair, which is the link between methylation and aging since DNA repair typically declines with increasing age.

The Molecular Mechanisms of Methylation

Another way to understand this process is by categorizing biological methylation as either DNA methylation or protein methylation. Yet, both can impact gene expression or activity. However, these two categorizations actually require different enzymes for each process to take place.

The Enzymes Involved in Methylation

The main enzymes involved in methylation are DNA methyltransferases and protein methyltransferases. Ultimately, the enzyme type depends on whether DNA or a protein molecule is being methylated. So, let’s briefly take a closer look at these two enzymes.

1. DNA Methyltransferases

DNA methyltransferases (DNMTs) are enzymes that catalyze the transfer of a methyl group from a donor molecule (usually S-adenosylmethionine, SAM) to the cytosine base in DNA, creating 5-methylcytosine (5-mC). In other words, DNMTs control gene expression through DNA methylation.

However, it’s worth noting that environmental and lifestyle factors can influence the activation or inhibition of these enzymes. In turn, our external environment and lifestyle choices impact how our genes are expressed and even our risk of certain diseases (5).

For instance, if we have “Gene X,” which helps our body’s cells absorb glucose effectively, lifestyle changes, such as poor diet or lack of exercise, may alter how this gene is expressed. Gene X may become hypermethylated (a type of abnormal methylation), potentially leading to insulin resistance, pre-diabetes, or diabetes. In turn, our body may not be able to use glucose very well, and we may be prone to high blood sugar. 

Yet, the opposite can also be true: If we adopt healthy lifestyle changes, like a balanced diet and regular exercise, this hypermethylation can be altered and return to normal. In turn, this individual generally experiences regulated and stable blood sugar levels.

2. Protein Methyltransferases

Protein methyltransferases are enzymes that transfer methyl groups from a methyl donor (often SAM) to target amino acids in the protein, such as lysine or arginine. Protein methylation can regulate various cellular processes, including gene expression, signal transduction, and protein-protein interactions.

Similar to DNMTs, certain factors can influence the activation or inhibition of these enzymes, impacting our body’s functions and gene expression. However, lifestyle or environmental factors can also alter genetic SNPs (Single Nucleotide Polymorphisms).

SNPs are variations in a single DNA building block or specific spot on the DNA. Common SNPs include MTHFR and COMT, which are broken down in more detail below.

      • The MTHFR gene is primarily responsible for the creation of an enzyme called methylenetetrahydrofolate reductase. This enzyme is essential for processing amino acids and converting folate into a usable form, which is necessary for the conversion of homocysteine to methionine. It also plays a crucial role in the metabolism of folate (vitamin B9), which is important for DNA synthesis, repair, and methylation. MTHFR mutation may lead to blood clotting issues, mental health disorders, learning problems, cancer, and other cardiovascular diseases.

      • The COMT gene provides instructions to make the enzyme catechol-O-methyltransferase, which is necessary to regulate levels of various hormones. If mutations in this gene occur, an individual may struggle with high levels of certain hormones, like dopamine, norepinephrine, and estrogen. Inevitably, this can lead to various imbalances, such as depression, anxiety, early menopause, infertility, low libido, and more.  

    The Role of Methylation in Gene Expression

    We all know that our DNA contains our genetic code. But RNA is what helps transcribe this code so that it can be translated into the creation of different proteins (AKA what our genes end up expressing). So, where does methylation come into play here?

    Well, as we know from the above, methylation can occur in DNA, RNA, and proteins. An easy way to think of how this works is that DNA methylation determines what genes are turned on or off. From there, RNA methylation fine-tunes these expressions even further—and the same goes for protein methylation. In turn, this means that methylation controls gene expression, determines genomic stability, and also plays a part in how our cells adjust and react to the external environment.

    Health Implications and Disease Associations 

    The big buzz around methylation is largely related to how this process can impact our health and longevity. In fact, decreased methylation, in some contexts, may mean increased diseases. 

    In recent years, the link between methylation and disease has become a major research topic—specifically when discussing how we can prevent the prevalence of modern diseases and disorders. So, what should you know? 

    Psychological Aspects of Methylation

    Methylation impacts our biology and genetics, but also our cognition, our mental health, and even our behaviour. So, let’s take a closer look at these lesser-known psychological aspects.

    Neurotransmitter Regulation

    Neurotransmitters are the body’s chemical messengers; they help messages transfer from one cell to another. Without getting too technical, methylation is suggested to impact neurotransmitters in various ways, including:

        • The production of neurotransmitters, such as serotonin, dopamine, and GABA (6).

        • How the body or brain responds to these neurotransmitters.

        • The balance of neurotransmitters, which can lead to the development of certain neurological disorders.

      Methylation and Mental Health

      Interestingly, methylation has also been an area of interest in mental health research and the development of psychiatric disorders. Specifically, DNA methylation may play a role in the emergence of:

          • Schizophrenia

          • Bipolar disorder

          • Major depressive disorder

          • Eating disorders (including anorexia and bulimia)

          • And alcohol use disorder

        Cancer and Abnormal Methylation

        Research goes on to link abnormal, or aberrant, methylation with an increased cancer risk. In fact, abnormal methylation is the most common type of “cellular lesion” found in human tumors. It’s suggested that this marker could help with early risk factors or cancer detection, potentially saving lives. 

        In particular, abnormal methylation of the COMT gene, as discussed above, can lead to issues with estrogen detoxification. This can increase estrogen levels in the body and, thus, the risk of breast cancer—indicating the importance of genetic testing and epigenetics work.

        Methylation and Cardiovascular Health

        Cardiovascular disease takes the top spot when it comes to the leading cause of death worldwide. While research shows that factors impacting methylation, such as smoking and air pollution, may increase cardiovascular risk, more research is currently needed to determine the exact mechanisms.   

        However, here’s what we do know: Higher levels of homocysteine, which often happen due to impaired methylation, contribute to increased inflammation. From here, chronic inflammation can increase our risk of cardiovascular disease, often due to damaged blood vessels. In turn, this can increase our risk of a heart attack or stroke.

        Methylation and Autism

        Abnormal methylation is further linked to the development of autism (with the prevalence of this disorder becoming increasingly common over the last 20 years). Research suggests that genetic and environmental factors may play a role in autism through methylation pathways. It’s thought this could serve as a useful biomarker for an autistic diagnosis. 

        Methylation and Fertility

        Methylation can impact both female and male fertility factors. It’s even linked with recurrent pregnancy loss or miscarriages.

        Methylation and Ageing

        Probably the most popularized aspect of methylation is the aging implications. Research shows that increased methylation is associated with accelerated aging, including increased disease and decreased repair or rejuvenation. Thus, it’s commonly used as a biomarker for aging and age-related diseases.

        List of Health Conditions Affected By Methylation

        Decreased or abnormal methylation has further been implicated in contributing to the following diseases:

            • Diabetes

            • Arthritis 

            • Multiple Sclerosis (MS)

            • Obesity-related conditions

            • Lupus

            • Cancer

            • Atherosclerosis

            • Heart disease

            • Alzheimer’s disease

            • Parkinson’s disease

            • Huntington’s disease

            • Epilepsy

            • Depression

            • Schizophrenia

            • Eating disorders

            • Alcohol-use disorder

            • Autism

            • Anxiety-related disorders

            • Infertility

            • Sexual dysfunction

            • Polycystic Ovarian Syndrome (PCOS)

            • Macular degeneration

            • Allergies

            • Asthma

            • Thyroid disorders or dysfunctions

            • Inflammatory bowel disease

          Environmental Influences on Methylation

          The interesting part about methylation is that we actually have some control. The environmental factors we are exposed to impact methylation and associated outcomes. These environmental influences include:

              • Diet

              • Exercise

              • Drugs/Medications

              • Chemical exposure

              • Stress

              • Pollution

            Epigenetics and Emerging Areas of Research and Treatment Strategies

            The good news is that all of this methylation research is also contributing to potential new therapies and treatments. And this all falls under the field of epigenetics.

            Epigenetics is the study of how external factors can change gene expression. This rapidly evolving field further looks at how these gene expressions may prevent or predict disease and help with disease management. Yet, researchers also take this a step further. More and more research emerges every day regarding how our genes might be the answer to increased longevity and health spans. 

             For instance, it’s suggested that epigenetic modifications involving methylation could eventually emerge as anti-cancer therapies. In other words, it could offer life-saving approaches to prevent and treat cancers, especially those that are high-risk or difficult to treat with current strategies.

            Yet, it could also help prevent various other diseases by serving as a key biomarker, helping to address health problems earlier. For example, autism is linked to methylation alterations in our genes. This means environmental factors, nutritional status during pregnancy, and early life exposures might impact these gene expressions, offering potential avenues for early intervention and therapy.

            Depression is also another major focus in the epigenetic world. Abnormal methylation, as discussed above, has been implicated as a potential factor contributing to depression. Yet, nutrients that support methylation, like B vitamins, magnesium, and SAMe, have been studied for their potential to improve depression symptoms and mood.

            As we know, cardiovascular disease is also an ever-looming threat in our modern world. However, epigenetics is also uncovering potential preventative pathways when it comes to heart disease. For example, we know managing homocysteine levels is key in order to prevent adverse health effects. Generally, this often comes down to a vitamin B deficiency in the diet. Thus, it’s suggested that increasing vitamin B6, B12, and folate may support normal methylation and reduce homocysteine levels. In turn, this may lower your risk of heart disease.

            Conclusion

            Research about methylation and our understanding of it continues to emerge, and it’s exciting! It could give way to new insights and therapies to improve health and prevent illness. As a result, this could be a key piece in people living longer and better lives—at least, it would appear we’re getting closer to this than ever before.

            • What does methylation do in the body? And how does it work?

              Methylation is an essential process in the body that determines how genes are expressed, how our cells function, and more. Methylation works by adding a methyl group to DNA, RNA, and proteins. As a result, genes are turned on and off, refined, and adjusted.

            • How does methylation impact gene expression?

              Methylation impacts gene expression by impacting whether or not DNA is transcribed by RNA and also how RNA transcribes and then translates that information. This, in turn, alters how the gene is expressed and whether or not it is expressed at all.

            • What role does methylation play in mental health?

              Normal methylation is essential for good mental health and cognitive function. Abnormal methylation, thus, may lead to various common mental health disorders and cause mood fluctuations.

            • Can methylation be influenced by lifestyle factors?

              Yes, environment and lifestyle factors can influence methylation and, thus, gene expression. 

            • How is aberrant/abnormal methylation linked to cancer?

              This abnormal methylation can increase the activity of the pathways that lead to cancer, such as tumor development. Abnormal methylation is further suggested as a potential early detector of cancer, which may help prevent and treat it before it becomes health-hazardous or life-threatening.

            Dr Menka Gupta

            IFMCP, MSc, MBBS

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