What Is Methylation, How Does It Affect Health and Aging?

MTHFR is the most studied gene in nutrigenomics. In fact, the methylation pathway plays a role in the conversion of homocysteine to methionine using folate, as well as in the processing of amino acids containing sulfur and the production of the main antioxidant glutathione. DNA methylation changes the human genome and can affect aging and many diseases.

What is Methylation?

In humans, methylation affects the cytosine (C) nucleotide. It is the process of binding of a methyl group (a carbon atom bound to 3 hydrogen atoms) to cytosine nucleotides. MTHFR, the most studied gene in nutrigenomy, is a key player in this process. People (only 4% of the population) with two copies of the C677T variant produce an enzyme with reduced activity by about 70%. The steps to convert folate to MTHF or methyltetrahydrofolate include many enzymes, including MTHFR, which are as follows:

• The methylation cycle begins with homocysteine

• One of the molecules affected in this way plays a role in DNA making

• Another enzyme, MTR or methionine synthase, converts homocysteine to methionine

• SAM-e has a methyl group that can cause DNA methylation where it can switch to DNA

• The final result of the methylation cycle is methionine, but it also produces other compounds that are important for antioxidant defense, such as glutathione, and affect folate metabolism.

Ways to open or close genes are often known, but their biochemical basis is not related to methylation: adding a methyl group is one way to turn a gene on and off. In normal cells, methylation provides proper gene activation and silencing. DNA methylation causes a significant change in the genome that plays a role in the regulation of many cellular processes. These processes include chromosome structure and stability, DNA transcription and embryonic development. However, if the methylation cycle is less efficient, homocysteine can accumulate as if the activity of MTHFR is reduced because it is not converted to a sufficient amount of methionine. High levels of homocysteine are a major risk factor for many diseases, from inflammation and heart disease to diabetes, autoimmune diseases (such as psoriasis), neurological problems, cancer and others.

Methylation Types

Methylation is the epigenetic basis for studying how the environment affects human genes. Environment, lifestyle and diet are factors that can turn genes on and off. The methylation and demethylation patterns presented here have an effect on chronic diseases such as health, aging and cancer. Excess or little methylation can be harmful, however, important genes and which one is open-clad should be considered. Enabling or disabling some key areas can have the most serious health complications (such as hypomethylation of repeat sequences in cancer).

DNA Hypermethylation

A healthy body has a certain level of methylation. Irregular and overmethylated DNA can replace a gene, meaning it prevents it from producing. Changes in the placement of methyl groups cause diseases. Some researchers have even used the amount of methylation in certain genes as a biological watch because its formation in individual genes is proportional to age. Functions where DNA hypermethylation is effective are, but not limited to:

• Causing cancer

• Reducing immune system function

• To harm brain health

• Reducing energy and exercise

• Fast aging

It can inactivate and reduce the expression of some tumor suppressor genes. In addition, external environmental factors can change methylation, and in other words, although the abnormal methylation in DNA can copy and pass itself, this balance can be changed by everything around.

DNA Hypomethylation

Too little methylation can also be harmful. If there is insufficient methylation in the body, it can cause genomic instability and cell transformation. And although hypermethylation is thought to be more common in cancers, newer research has revealed that hypomethylation also plays a role in these conditions. Hypomethylation is beneficial for short-term cancer, but it also accelerates cancer growth. Methylation in cancer is defined as too much but too little. In cancer, some parts of DNA are over-methylated, while some parts are normalmethylated, resulting in a complete imbalance in the methylation cycle. In addition to cancer, hypomethylation contributes to inflammation, leading to autoimmune diseases such as atherosclerosis, lupus and multiple sclerosis.

DNA Demethylation

DNA demethylation also plays a role in tumor formation, but this process is very important during embryo development. Scientists have long struggled to understand how complex biochemical messages are delivered to the embryo to enable identical stem cells to transform into specialized cells, tissues, and organs. Demethylation takes place in early embryos and is required to separate stem cells into specific cell types. DNA regions are opened or closed and then modified by demethylation to ensure healthy development. Also demethylation eliminates the modification of DNA nucleotides.

Methylation and Aging: Epigenetic Clock

Methylation is not a black-and-white, symmetrical phenomenon, and it’s not just about DNA being more or less methylated, it’s about how it works. It turns out that methylation increases in childhood, where most of this process takes place. By age, CpG islands are becoming overmethylated only in certain regions of the DNA, while the rest is undermethylated, and this is the hallmark of aging. Based on the CpG methylation model, scientists estimate the age of one today. This is called an epigenetic watch, a biomarker of aging based on a specific progressive methylation pattern common to most people who tell us about functional age. However, each individual has a so-called epigenetic drift, which is generally under investigation, slightly different from the general population. Basically, based on the DNA methylation scheme, scientists say the epigenetic age and compare it to the real age. Based on this, it is possible to be younger or older epigenetically, and if the person is epigenetically older, this indicates a greater chance of greater health problems.