Methylation – How Does It Affect Our Health & Aging?

Managing Your Genes: Understanding Methylation

Methylation - How Does It Affect Our Health & Aging?

You probably realize that your genes can predispose you to certain diseases, and that if you have a “faulty” gene, this is something you inherit at birth.

However, you may not realize that our genes are constantly affected by our environment, our lifestyles and our nutrition and can be influenced by these factors either to be more expressive or to be less active.

Methylation is one of the important epigenetic processes by which gene activity is turned on or off, up or down, often in response to environmental triggers and  can then impact our health. 

Epigenetics is the study of changes to an organism caused by modification of gene expression, rather than by changes to the DNA itself.

In other words, these changes affect our health by “dialing” genes activity up or down without altering the genes. As methylation affects how genes express, methylation can accelerate disease or slow it down or stop it.

It’s important to have the right amount of methylation …. Not too much and not too little.

There are other processes that modify gene expression through epigenetics, such as histone modifications, but methylation is our focus for , lead and Bisphenol A (BPA), understanding the effects and accumulation of these toxins is essential. Many toxins including lead and BPA inhibit the function of methyltransferases, plus, mercury inhibits methionine synthase, which also affects methylation. Most of the time people don’t even realize they are being exposed.

Methylation plays an essential role in the detoxification processes, such as the elimination of heavy metals. As it also plays a role in the generation of neurotransmitters, certain mental health conditions might be affected by methylation patterns. When methylation is addressed, it can help with recovery and prevention.

Interpreting test results can require expertise. To assess how a specific individual will be affected it is necessary to develop a clear picture of SNP effects, which may involve further metabolic tests, combined with evaluation of the person’s symptoms and responses to previous medical interventions.

Identifying SNPs that influence health and disease risk allows clinicians to support their patients with appropriate lifestyle and nutrition changes to maximize health and wellness and help the patients be proactive about their health.

What is MTHFR?

One of the first methylation SNPs to be identified was Methylenetetrahydrofolate reductase (MTHFR SNP). When methylation was becoming a focus of functional health, MTHFR was identified is an important methylation enzyme.

It is responsible for the activation of folate for the subsequent reduction of homocysteine to methionine. Certain single nucleotide polymorphisms (SNPs), or variants of this gene, result in the reduced capacity of this enzyme.

Indeed, MTHFR variants are associated with increased risk for many diseases, including depression, fertility issues, insomnia, and thyroid conditions.23 and me

Having an MTHFR variant (SNP) might not indicate you need serious medical treatment, it could just mean you need to take the right supplemental vitamin B. Sometimes, instead of genetic testing, high homocysteine levels in blood testing can be used for screening and to assess the appropriate treatment.

Folate (B9) is a naturally occurring nutrient found in many foods and the body naturally converts it into the methylated form.

When an MTHFR SNP is present that natural conversion is limited, so it can be helpful to take the Methyltetrahydrofolate supplement or prescription, which is folate that is already methylated — so it’s in the form the body can use more readily. Changing to the bioavailable folate is often a step in the right direction.

How can testing for methylation help us diagnose diseases better?

Much progress has been made in understanding methylation patterns particularly in cancer scenarios. Smoking can lead to a huge amount of extra methylation, leading in turn to an increased risk for a variety of conditions including lung cancer.

Unfortunately for the people who develop lung cancer, though, they often only learn about it because they start showing symptoms. By this time, the cancer may be very difficult to treat.

Epigenetic testing is currently being explored as a way of screening for patterns of gene regulation that indicate cancer at extremely early stages that are easier to address. For example, it may soon be possible for a doctor to ask a patient to cough into a specially designed collection tube to detect methylation patterns to check for lung cancer much before symptoms have presented.

How do diet and supplements affect methylation?

Nutrient deficiency is one of the principal reasons for methylation issues. Two important nutrients that influence methylation pathways are Vitamin B12 and folate (B9).

However, other nutrients such as methionine, cysteine, taurine, zinc, magnesium, potassium, riboflavin (B2) and niacin (B3), also play substantial roles. Insufficient intake of these nutrients can affect useful methylation.

Foods rich in these nutrients, such as spinach, mushrooms, beets, eggs, organ meats and shellfish, can support methylation.

How do you treat methylation imbalances?

Typically, I first address nutrient imbalances as I also recommend adding specific nutrients and foods to a daily diet. But I also recommend promoting a healthy gut biome to bring intestinal bacteria back into balance.

I often also check for toxin levels, as environmental stresses can cause some methylation pathways to go into overdrive, which calls for them to be rebalanced.

The patient might also be taking medication for another condition, which could affect the methylation pathway.

So to sum up, when checking for methylation patterns I often follow these steps:

  1. Order a methylation pathway test and methylation gene test
  2. Test for nutrient deficiencies
  3. Test for toxins
  4. Identify medications which could compete with methylation
  5. Test microbiome balance and,
  6. Retest above as needed

Then we take steps to rebalance the methylation processes through diet and nutrition. Sometimes I also prescribe plant adaptogens. These contain molecules that are very powerful for rebalancing the body.

Plant adaptogens include phytonutrients such as curcumin, betanin, anthocyanins, quercetin, and lycopene, all of which are abundant in a balanced, nutrient-dense diet, but additional supplementation is still helpful in some cases.

How is methylation associated with aging?

The study of methylation patterns is already indicating differences between healthy versus unhealthy aging. For example, methylation patterns of an individual can predict biological age better than chronological age.

Emerging data shows that aging is accompanied by a decline in methylation patterns, along with specific methylation of certain stretches of DNA. Methylation is postulated to play a role in longevity, and while there is still much to learn about methylation, as this is reversible change to our DNA it is a highly appropriate target for disease intervention.

Eventually, methylation patterns will almost certainly be commonly used as a predictor for your health, your predisposition to disease and even your aging. This is why it is very important to understand your methylation to get a jump start to optimize your health.

Source: https://annshippymd.com/teach-your-genes-to-behave/managing-your-genes-understanding-methylation/

Epigenetic aging is accelerated in alcohol use disorder and regulated by genetic variation in APOL2

Methylation - How Does It Affect Our Health & Aging?

To investigate the potential role of alcohol use disorder (AUD) in aging processes, we employed Levine’s epigenetic clock (DNAm PhenoAge) to estimate DNA methylation age in 331 individuals with AUD and 201 healthy controls (HC).

We evaluated the effects of heavy, chronic alcohol consumption on epigenetic age acceleration (EAA) using clinical biomarkers, including liver function test enzymes (LFTs) and clinical measures.

To characterize potential underlying genetic variation contributing to EAA in AUD, we performed genome-wide association studies (GWAS) on EAA, including pathway analyses. We followed up on relevant top findings with in silico expression quantitative trait loci (eQTL) analyses for biological function using the BRAINEAC database. There was a 2.

22-year age acceleration in AUD compared to controls after adjusting for gender and blood cell composition (p = 1.85 × 10−5). This association remained significant after adjusting for race, body mass index, and smoking status (1.38 years, p = 0.02).

Secondary analyses showed more pronounced EAA in individuals with more severe AUD-associated phenotypes, including elevated gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT), and higher number of heavy drinking days (all ps  0.

05), as a dependent variable and AUD diagnosis as an independent variable with gender and blood-cell type composition as covariates (basic model). The fully adjusted model included additional covariates for race, smoking status, and body mass index (BMI).

Race, as determined by ancestry-informative markers score (AIMs), was included because race/ethnicity has previously been shown to be associated with epigenetic aging [23]. Smoking status was included to account for potential confounding lifestyle factors affecting aging due to the disproportionately high concurrence of smoking in the AUD individuals compared to HCs groups [24]. Furthermore, BMI has previously been shown to predict accelerated epigenetic aging [25]. Blood-cell counts were included as covariates to correct for differences in blood cell-type composition between individuals [26, 27].

For exploratory analyses, additional linear regression models that were adjusted for all covariates were used to examine the relationship between EAA and the number of heavy drinking days in a 90-day window (≥4 drinks a day for females; ≥5 drinks a day for males) within individuals with AUD.

To further dissect the AUD phenotype, we examined EAA in the most and least severe cases defined by the third (highest) quartile and the first (lowest) quartile of each respective biomarker level (GGT, ALT, AST, and ALP level) in the AUD group.

Linear regression models were used to compare the EAA between samples in the highest and lowest quartiles of each biomarker. Statistical analyses were performed in R version 3.5.1.

GWAS analysis for epigenetic age acceleration

A genome-wide association study (GWAS) was performed in European Ancestry (EA) and African Ancestry (AA) participants separately with the Illumina OmniExpress and Illumina OmniExpressExome BeadChips (Illumina, San Diego, CA).

Ethnicity for each individual was characterized using a panel of 2500 AIMs, which were then compared to the 51 worldwide populations represented in the Human Genome Diversity Cell Line Panel of the Human Genome Diversity Project (HGDP) and Centre d’Etude du Polymorphisme Humain (CEPH), which includes 1051 individuals (http://www.cephb.fr/HGDP-CEPH-Panel) [28].

Ancestry scores were calculated using Structure, version 2.2 (https://web.stanford.edu/group/pritchardlab/structure.html) where data for the CEPH diversity panel were run along with our samples using the AIMs [29]. The ancestry scores for six ethnic factors (Africa, Europe, Asia, Far East Asia, Oceania, and Americas) were then estimated for each subject.

the 6 ethnic AIM scores, we identified EA by having a European AIM score of 80% or greater and AA participants by having an African AIM score of 20% or greater and AIM scores for other races of 5% or lower.

the genetically identified EA and AA individuals, we conducted a series of quality control (QC) procedures within each race group including: sex check by X chromosome, Hardy–Weinberg equilibrium (HWE) test in a control sample in EA and AA separately (P > 0.0001), missingness by SNP (missing rate

Source: https://www.nature.com/articles/s41386-019-0500-y

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