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Methylation – How Does it Affect Our Health & Aging?

Written by Joe Cohen, BS | Last updated:
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Joe Cohen, BS | Last updated:

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Did you know that MTHFR is the most studied gene in nutrigenomics? In fact, the methylation pathway is involved in the conversion of homocysteine to methionine, using folate. It is also involved in the processing of sulfur-containing amino acids and the production of glutathione, our major detoxifying enzyme. DNA methylation modifies the human genome, affects aging, defines our “epigenetic clock” and can influence many diseases. Read more below to learn more.

Get the free Methylation Special Report

What Is Methylation?

I recently discovered that I am homozygous for the C677T – this variation is present in only 4% of the population. And with this mutation, the enzyme function could be reduced by about 70%. It might explain some of the health issues that I have dealt with.

But what exactly is methylation?

Methylation in humans affects the cytosine (C) nucleotide. It is the process by which a methyl group (a carbon atom with 3 hydrogen atoms attached to it) connects to the cytosine nucleotides [1].

The steps to converting folate to MTHF or methyltetrahydrofolate involves many enzymes, including MTHFR.

  • The methylation cycle starts with homocysteine.
  • One of the molecules affected in this pathway is involved in making DNA.
  • Another, MTR or methionine synthase, converts homocysteine to methionine. It needs vitamin B12 and 5-MTHF to function.
  • SAM-e has a methyl group attached to it, which it can “give” to our DNA, causing DNA methylation.
  • The end result of the methylation cycle is methionine, but also produces other compounds important for antioxidant defense and affects folate metabolism.

We often hear about ways to “turn on” or “turn off” genes, but the biochemical basis on it is methylation: adding a methyl group is one way of turning on and off a gene. In normal cells, methylation ensures this proper gene activation and silencing. DNA methylation causes a crucial modification to the genome that is involved in regulating many cellular processes. These processes include chromosome structure and stability, DNA transcription, and embryonic development [1, 2].

But if the methylations cycle is less efficient – like if the activity of your MTHFR is reduced – homocysteine can build up because not enough of it is being converted to methionine. High homocysteine levels are a big risk factor for many diseases – from inflammation and heart disease to diabetes, autoimmune diseases (like psoriasis), neurological issues, cancer, and others [3].

If youre curious to read more, download the Methylation Bonus that goes in-depth about the science, specific SNPs to look out for, and how I was able to overcome my MTHFR issues.

Get the free Methylation Special Report

Types of Methylation

Methylation is the basis of epigenetics, the study of how the environment affects our genes. Our environment, our lifestyle, and diet are all factors that can turn genes on or off. The patterns of methylation and demethylation presented here can have an impact on health, aging, and chronic disease like cancer [4].

Although over and undermethylation can both be harmful, its important to consider which genes are being turned on or off“. Activating or deactivating some key regions can have the most serious health complications (such as hypomethylation of the so-called repeat sequences in cancer) [5].

1) DNA Hypermethylation

A healthy body has a certain level of methylation. Irregular and over-methylated DNA can change a gene, preventing it from producing what its meant to. Changes in the placement of methyl groups can cause diseases [6].

Some researchers have even used the amount of methylation in certain genes as a biological clock, as it occurs in individual genes is proportional to age. The implications include, but are not limited to:

  • Causes cancer
  • Lowers immune system function
  • Damages brain health
  • Lowers energy and exercise
  • Quickens aging

It can inactivate certain tumor-suppressor genes and stop the expression of mRNAs that play a role in tumor suppression [2].

Additionally, external, environmental factors can alter methylation. In other words, while abnormal methylation in DNA can replicate itself and be passed down, this balance can also be altered by everything around us [6].

2) DNA Hypomethylation

Too little of methylation can also be harmful.

If there is insufficient methylation in the body, it can cause genomic instability and cell transformation [2].

And although hypermethylation was thought to be more common in cancers, cancers seem to equally have hypomethylation. Hypomethylation can be beneficial for cancer short-term, but it may also speed up cancer growth [7].

This methylation in cancer has been described as too much, but too little“. In cancer, some parts of the DNA are overmethylated, and other parts undermethylated, leading to a complete dysbalance of the normal methylation cycle [8].

And aside from cancer, hypomethylation may also contribute to inflammation (leading to atherosclerosis) and autoimmune diseases, such as lupus, multiple sclerosis [5].

3) DNA Demethylation

DNA demethylation can also play a role in the formation of tumors [9].

But during embryo development, this process is crucial. Scientists have long struggled to understand how complex biochemical messages are communicated in the embryo to enable identical stem cells to develop into specialized cells, tissues, and organs. Demethylation happens in early embryos and is essential for stem cells to be able to differentiate into different cell types. Parts of DNA are turned on or off, and then modified via demethylation again for healthy development to take place [10].

Demethylation removes the modification of the nucleotides from DNA [6].

Methylation And Ageing: the “Epigenetic Clock”

Methylation is not a black-or-white phenomenon. It’s not symmetrical in any way. And it’s not just a matter of if your DNA is more or less methylated, but how. It turns out that methylation increases during childhood, but most of the DNA is being methylated at that time. As we age, just the specific regions of DNA, the CpG islands become overmethylated while the rest of the DNA is undermethylated. This is the hallmark of aging [11].

Based on the pattern of CpG methylation, scientists can now predict someone’s age. This is called the epigenetic clock” – a biomarker of aging – the specific methylation pattern of aging common to most people that tells us about our “functional age”. But there is also a “drift” in each individual, a pattern slightly different in each person from the general population, called the “epigenetic drift” that is still being explored [11].

Basically, based on your DNA methylation, scientists might be able to tell you your “epigenetic age” and compare it to your actual age. Based on this, you could be epigenetically younger or older. And if you’re epigenetically older, then this points to a greater chance of health problems [11].

About the Author

Joe Cohen, BS

Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.Frustrated by the lack of good information and tools, Joe decided to embark on a journey of self-experimentation and self-learning to improve his health--something that has since become known as “biohacking”. With thousands of experiments and pubmed articles under his belt, Joe founded SelfHacked, the resource that was missing when he needed it. SelfHacked now gets millions of monthly readers.Joe is a thriving entrepreneur, author and speaker. He is the CEO of SelfHacked, SelfDecode and LabTestAnalyzer.His mission is to help people gain access to the most up-to-date, unbiased, and science-based ways to optimize their health.
Joe has been studying health sciences for 17 years and has read over 30,000 PubMed articles. He's given consultations to over 1000 people who have sought his health advice. After completing the pre-med requirements at university, he founded SelfHacked because he wanted to make a big impact in improving global health. He's written hundreds of science posts, multiple books on improving health, and speaks at various health conferences. He's keen on building a brain-trust of top scientists who will improve the level of accuracy of health content on the web. He's also founded SelfDecode and LabTestAnalyzer, popular genetic and lab software tools to improve health.

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