Longevity Articles

The Basics of Methylation and Why It's Important For Healthy Aging

The Basics of DNA Methylation and Why It's Important For Healthy Aging

While much of the conversation in the longevity community is centered around increasing NAD+ levels and activating sirtuins (longevity genes), there is an important biochemical process that often gets overlooked. This process, known as methylation, occurs in all living cells and plays a role in several aspects of aging, including DNA repair, cell signaling and metabolism.

The methylation process is also responsible for many other important functions in the body, such as:  

  • Forming neurotransmitters
  • Producing free radical-scavenging antioxidants
  • Clearing histamine
  • Cell division
  • Cellular energy production
  • DNA expression (epigenetics)

The Basics of Methylation

In scientific terms, methylation is the addition of a methyl group (CH3—a carbon atom attached to three hydrogen atoms) to DNA or other molecules within cells. DNA methylation regulates cellular aging by turning on or off the expression of certain genes. If the DNA methylation process is not functioning optimally, genes related to accelerated aging may become activated. Studies show that individuals with poor methylation are at higher risk for age-related health decline (1).

In our bodies, we have a “methyl pool,” a storage center of sorts, containing CH3 methyl groups that our body uses whenever transfers need to be made in certain biochemical processes. If we have enough methyl groups stored up, methylating typically takes place without issue. However, there are a variety of factors that can affect the methylation process, and how well it performs. Below are some of the factors that affect healthy methylation patterns.

Factors that Affect Methylation Potential

Environment: The methylation process can be altered over time due to environmental factors such as diet, stress levels, toxin exposure and more, leading to epigenetic changes that impact how certain genes are expressed. Supporting healthy methylation is a good way to make sure longevity-promoting genes remain actively expressed.

Genetic mutations: MTHFR gene variants are prevalent in up to 40% of certain populations and can cause disturbances in the methylation process (2). Oftentimes, supplementing with methylated B vitamins or other methyl donors, such as TMG, is all that is necessary to support methylation in these individuals.

Aging: Methylation ability and healthy expression of longevity-promoting genes declines with age. Supporting methylation with methyl donor nutrients is a good way to promote healthy gene expression with age. 

Supporting methylation with methyl donor nutrients is a good way to promote healthy gene expression with age.

Methyl Donor Nutrients

There are several nutrients known to support proper methylation processes: methylfolate (vitamin B9), methylcobalamin (vitamin B12), betaine/trimethyglycine (TMG), choline, magnesium, zinc and S-adenosylmethionine (SAMe). Methylfolate is well studied due to its role in DNA synthesis while SAMe activates enzymes involved in detoxification within cells. 

Perhaps the most popular methyl donor supplement used in the longevity community is TMG. TMG is a methyl donor nutrient that plays a role in liver function, cellular reproduction and helping make carnitine, which naturally decreases with age. TMG also helps the body metabolize the amino acid homocysteine, which can contribute to damage within the arteries and heart health issues if present in high amounts.

Some research suggests individuals supplementing with NMN should also supplement with TMG to prevent a potential depletion of methyl donor nutrients.

Read our full article here on the benefits of TMG and why TMG may be the perfect complement to NMN.

Main Takeaway

In conclusion, the methylation process plays a critical role in the regulation of gene expression and influences a wide range of biological processes, including aging and longevity. DNA methylation, in particular, has been shown to change with age, contributing to the aging process itself.

Due to the fact that methylation issues increase with age, it is especially critical for individuals over the age of 40 to optimize lifestyle factors such as sleep, diet and stress management to ensure healthy methylation patterns. Additionally, supplementing with methyl donor nutrients such as TMG may be helpful to combat issues related to poor methylation. 


  1. Johnson AA, Akman K, Calimport SR, Wuttke D, Stolzing A, de Magalhães JP. The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation Res. 2012;15(5):483-494. doi:10.1089/rej.2012.13242
  2. Graydon JS, Claudio K, Baker S, et al. Ethnogeographic prevalence and implications of the 677C>T and 1298A>C MTHFR polymorphisms in US primary care populations. Biomark Med. 2019;13(8):649-661. doi:10.2217/bmm-2018-0392

Older post Newer post