What is methylation?
Methylation in humans affects the nucleotide cytosine. It is a process whereby a methyl group (a carbon atom with three hydrogen atoms attached to it) binds to cytosine nucleotides.
MTFHR, the most widely studied gene in nutrigenomics, is a key player in this process. The stages of converting folate into MTHF or methyltetrahydrofolate involve numerous enzymes, including MTHFR.
The methylation cycle starts with homocysteine. One of the molecules involved in this pathway is crucial for DNA synthesis. Another, MTR or methionine synthase, converts homocysteine into methionine. It requires vitamins B1, B2, and 5-MTHF for its function.
K-SAMe has a methyl group attached to it, which it can "transfer" to our DNA, inducing DNA methylation. The end result of the methylation cycle is methionine, but it also produces other compounds important for antioxidant protection, such as glutathione, and influences folate metabolism.
We often hear about ways to "turn on" or "turn off" genes, but not about the biochemical basis of this methylation: adding a methyl group is one way of turning genes on and off. In normal cells, methylation ensures proper gene activation and suppression. DNA methylation brings about critical modifications to the genome that participate in regulating many cellular processes. These processes include chromosome structure and stability, DNA transcription, and embryonic development.
But if the methylation cycle is less efficient – for example, if MTHFR activity is reduced – homocysteine may accumulate because it is not adequately converted to methionine. High levels of homocysteine are a serious risk factor for many diseases – from inflammation and heart disease to diabetes, autoimmune diseases (such as psoriasis), neurological issues, cancer, and other problems.
Types of Methylation
Methylation is the foundation of epigenetics, the study of how the environment influences our genes. Our environment, lifestyle, and diet – all these are factors that can turn genes on or off. The patterns of methylation and demethylation presented here can influence health, aging, and chronic diseases.
Although excess and insufficient methylation can be harmful, it's important to consider which genes are "turned on" or "turned off." Activation or deactivation of certain key areas can lead to the most serious health complications.
DNA Hypermethylation
A healthy organism has a certain level of methylation. Improper and excessively methylated DNA can alter a gene, preventing it from performing its intended function. Changes in the placement of methyl groups can cause diseases.
In diagnosis, the amount of methylation in specific genes can be used as biological clocks, as its frequency in individual genes is proportional to age.
The consequences of DNA hypermethylation lead to:
Oncological diseases.
Reduced immune system functions.
Impairment and damage to the brain.
Decreased energy.
Acceleration of aging processes.
Metabolism disorders.
Other pathologies.
Environmental factors can alter methylation. In other words, abnormal DNA methylation can self-replicate and be inherited, and this balance can also be altered by everything that surrounds us.
DNA Hypomethylation
Too weak methylation can also be harmful. If there is insufficient methylation in the body, it can cause genome instability and cell transformation. And although hypermethylation was thought to be more common in cancerous conditions, later research showed that hypomethylation also plays a role in these states. Hypomethylation can cause pathological conditions in the body.
Methylation in cancer has been described as "too much, but too little." In cancer, some DNA regions are overly methylated while others are insufficiently methylated, leading to a complete imbalance in the normal methylation cycle. Besides cancer, hypomethylation can also contribute to inflammation, leading to atherosclerosis, autoimmune diseases such as lupus and multiple sclerosis, and other diseases.
DNA Demethylation
DNA demethylation can also play a role in tumor formation. But during embryo development, this process is crucial. Scientists have long sought to understand how complex biochemical signals are transmitted to the embryo, allowing identical stem cells to develop into specialized cells, tissues, and organs. Demethylation occurs in early embryos and is necessary for stem cells to differentiate into specific cell types. DNA regions are turned on or off, and then modified again through demethylation to ensure healthy development.
Methylation and Aging:
Methylation is not a black-and-white symmetrical phenomenon. It's not just about how methylated your DNA is, but also about how it occurs. Methylation intensifies during childhood, when most of this process takes place. As you age, only certain DNA regions, CpG islands, become excessively methylated, while others are undermethylated. This is a sign of aging.
Essentially, based on the methylation patterns of your DNA, it is possible to determine your "epigenetic age" and compare it with your actual age. From this, you can be epigenetically younger or older. And if you are epigenetically older, it may indicate a greater likelihood of health problems.
I want to emphasize that blindly taking supplements is not advisable. For example, doctors often prescribe folic acid supplements to women, but if there's a mutation in the MTHFR gene, the enzyme's activity will be reduced (depending on the type of mutation, whether it's heterozygous or homozygous, and mutations in other genes), and the conversion to the active form will be low, leading to elevated homocysteine levels (hyperhomocysteinemia) and resulting pathologies. In the case of this mutation, methylfolate (the active form of B9) is prescribed. It's also important to understand that by taking one type of vitamin, you may create a deficiency in another. This especially applies to B-group vitamins.
Detecting mutations allows for supporting and restoring metabolism, correcting mental state, and preventing the development of pathological conditions, including oncology, by properly compensating for deficiencies in methylation. This is achieved through complexes of amino acids, vitamins, and minerals in a properly selected form and dosage.