Health

Turning Back the Methylation Clock Naturally – Becoming Younger?

Some of the most accurate ways of determining our biological age (as opposed to our chronological age) are through epigenetic clocks.  A recent study suggest that it may be possible to turn back our epigenetic clock through natural means and experience a rejuvenating effect.  Indeed, in just 8 weeks the study participants were able to turn back their epigenetic clocks 2-3 years.

In this article we will see what we can take from that study and possibly apply to our lives.

What Are Epigenetic Clocks?

One of the original, and still used, epigenetic clocks is the Horvath clock.  This is a methylation clock.  It looks at the methylation patterns of our DNA (DeoxyriboNucleic Acid).  So…

What is DNA Methylation?

Our DNA has our genetic code.  How the DNA is folded and packaged around proteins called histones decides which of our genes will be expressed at a given time.  This is epigenetics.

How the DNA is folded, and what genes are expressed, is in part decided by the methylation patterns we have.   DNA methylation is when a methyl group (CH3) is added to cytosine.  Cytosine is one of the four different nucleobases (Adenine, Thymine, Cytosine, Guanine, – A, T, C, G,  in the picture below) of our DNA.

The addition of methyl groups, or methylation, is carried out by DNA Methyl Transferases (DNMT).  They use S-Adenosyl methionine (SAM) as a source of methyl groups.

The de-methylation, when a methylated cytosine eventually gets back to regular cytosine, is initially carried out by Ten-Eleven Translocation (TET) demethylases.

Each cell type  (muscle cell, liver cell, neuron, etc) has a unique methylation pattern.  This is why, even though the DNA is the same in all of our cells, the expression of it is different in different cells.  A muscle cell expresses as a muscle cell and not as say, a liver cell.

Beyond the set methylation pattern for a particular cell type there are other methylation patterns.

Overall there are over 20 million methylation sites on the human genome and a few thousand of them are related to ageing.

In cancer, for instance, there are some particular sites that become hypermethylated, have too many methyl groups, while most of the genome will become hypomethylated, have too few methyl groups.

Thus for optimal methylation one would like to make sure to have methyl-donors so that there are methyl groups around when needed, and make sure that DNMT and TET work well so that the sites that need to be methylated will be methylated and those that need to be de-methylated can be de-methylated.

At this point we do not really know if the methylation pattern has causal impact on biological ageing or if it is only very well correlated with ageing.  However, as we shall see, there is a pilot study that suggests in favor of causality.

Epigenetic Methylation Clocks

The methylation clocks look at the sites that are related to ageing and look at the methylation patterns there.  Based on these patterns they can, quite accurately, tell the biological age.  

The first and most studied age-related methylation clock was developed in 2013 and is known as the Horvath clock.

Since then, other clocks have been proposed.  One such is the GrimAge clock, which is surprisingly accurate when it comes to predicting when a person will die.  

Can We “Reverse” the DNA Methylation Clock by Affecting Methylation Through Diet and Lifestyle Changes?

Recently a research group did a pilot study on this and got some positive results.

43 men aged 50-72 years old were involved and compared to a group without intervention.  

The result was that after 8 weeks of intervention the Horvath clock showed a decreased biological age by 3 years, compared to the comparison group, and 2 years, compared to the average age of the same individuals before the intervention.

We shall take a deeper look at what was actually done in the study.  But before we do that it is interesting to note that blood levels of health markers were also measured in the participants and they also improved.  This would suggest that reversing the Horvath clock we also, in fact, affect the biological ageing in the body, thus suggesting a causal link.

Below you will be able to see the different action steps that were taken in the study.

Diet

The diet in the study was a largely plant based and nutrient rich diet, with limited carbohydrates and mild fasting.  

Greater amounts of animal protein activate mTOR and increase the IGF-factor.  A primarily plant-based diet reduces this comparatively.

The limitation of carbohydrates and the fasting (a minimum of 12 h/day) were devised to reduce high blood sugar. 

High blood sugar, and/or a higher IGF-factor can drive cells into senescence, where some 30-70% then lead to pro inflammatory secretions, etc. 

Then care was taken to provide the body with methyl-groups and optimise, using current best practice, the functions of the enzymes involved in the methylation pathways.

Improve the function of TET

It has been shown that taking the right amount of vitamin A and C will reprogram cells back to their original methylation patterns by potentiating the activity of TET demethylases.  

The action step is to make sure to have vitamin C and vitamin A in your diet. They work synergistically in this case.

A precursor to vitamin A is found in red or orange foods, like tomatoes, carrots or pumpkins.  Vitamin C will be found in most fruits and vegetables.  To add more vitamin C you can add rose hip, fresh parsley, or if you live in a warmer climate citrus, or in tropical climates fresh acerola or camu-camu or dried powders of them.

Improve the Function of DNMT

DNMT carries out methylation.  By adding certain polyphenols it is possible to modulate its activity.

The action step is to take substances like curcumin, Epigallocatechin Gallate (EGCG), rosmarinic acid, quercetin, or luteolin.

Rosmarinic acid can be found in rosemary, curcumin can be found in turmeric, and EGCG is found in green tea (steeped for 10 min).

Ensure You Have Methyl-Donors

Have food rich in substances that contain methyl-groups.  These can be substances like folate, methylocobalamin (a form of B12), Trimethylglycine (betaine).

To get Trimethylglycine naturally it can be interesting to include red beets in the diet.

It is always more interesting to find foods containing the nutrients than to take supplements, as these may be associated with increased risks of disease.  Some studies have, for instance, found that a supplement of folic acid may lead to an increased risk of cancer, whereas a dietary increase of folic acid has the inverse effect.

Also, in particular, S-Adenosyl methionine (SAM) is involved in the methylation process, as the DNMTs use it as a methyl donor to methylate DNA.  

It turns out that shiitake mushrooms seem to somehow be able to elevate SAM and DNMT and improve methylation.  So, shiitake are considered methylation adaptogens.

They can also reduce blood homocysteine, which can be high when there is a lack of methyl-donors.  It is perhaps rather well known that high homocysteine is associated with heart disease.   And elevated homocysteine also seems to be associated with an insufficiency in methylation.

Cruciferous veggies, like broccoli, are also considered methylation adaptogens due to substances such as sulforophane (created in broccoli, especially in raw broccoli sprouts) and due to folate content.

Probiotics

Certain probiotics, such as in particular lactobacillus planetarium 299v, are folate producers and can alter gene expression.  They can also help maintain the gut-lining. 

Lactobacilli in general, use up folate, but lactobacillus planetarium produces it in the presence of Para-AminoBenzoic Acid (PABA).

Sleep

In the study it was recommended to get at least 7 hours of sleep each day because 7 hours is considered healthy.

There are studies showing that insomnia and pronounced lack of sleep lead to advancement in methylation clocks.

Exercise

In the study the participants did at least 30 min of exercise each day at 60-80% exertion.

This is because studies before the development of the Horvath clock show positive effects on methylation patterns as a result of exercise.  One such study was done on tai chi and another on women exercising.

Relaxation

It has been shown that prolonged stress affects methylation clocks and ageing.

The participants in the study did daily breathing exercises to relax.

The exercises they used were Steps to Elicit the Relaxation Response developed by Herbert Benson MD, twice daily.  The following instructional steps are taken IntegrativeTouch.org.

1.   Sit quietly in a comfortable position.

2.  Close your eyes.

3. Deeply relax all your muscles, 
beginning at your feet and progressing up to your face. 
Keep them relaxed.

4.  Breathe through your nose. 
Become aware of your breathing. Focus on a word, phrase, short prayer, or only your breathing. If you choose for example the word “one”
As you breathe out, say the word, “one”, 
silently to yourself. For example, 
breathe in … out, “one”,- in .. out, “one”, etc. 
Breathe easily and naturally.

5.  Continue for 10 to 20 minutes. 
You may open your eyes to check the time, but do not use an alarm. 
When you finish, sit quietly for several minutes, 
at first with your eyes closed and later with your eyes opened. 
Do not stand up for a few minutes.

6.  Do not worry about whether you are successful
in achieving a deep level of relaxation. 
Maintain a passive attitude and permit relaxation to occur at its own pace. 
When distracting thoughts occur, 
try to ignore them by not dwelling upon them
and return to repeating “one.”

With practice, the response should come with little effort. 
Practice the technique once or twice daily, 
but not within two hours after any meal, 
since the digestive processes seem to interfere with
the elicitation of the Relaxation Response.

Your Action Plan

If this dietary and lifestyle works for you, which a health consultant should be able to tell you, and you want to try it out, then here are the exact instructions from the study.

And here are some of the key details in picture form to inspire you on your youthful path.

The above are some things you may consider including in your day.  It is also helpful to eliminate candy, grains, dairy, and always have at least 12 hours without food, at night.

How Do I Know if it is Working?

Ideally you would check your epigenetic age before and after your lifestyle change.

Epigenetic clock measurements are often based on blood samples (though tests for other tissues have also been developed) and have so far been quite expensive for the individual.

However, at this time there is a trial going on at Dr. David Sinclair’s company Tally Health, of a new simple and inexpensive at-home test.  Hopefully, soon this test will be available so that we can measure our epigenetic ages and see if our health measures are affecting it positively.

References to studies are found by clicking the links in the text.

Images are taken from, or created with the help of, images from Unsplash.com.

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