TERT

TERT codes for part of the telomerase enzyme (hTERT), which can prevent damage to DNA. Telomerase is an enzyme that lengthens telomeres, the sequences of protective DNA at the ends of chromosomes. Cells with shortened telomeres can’t divide, and mice that received gene therapy to increase TERT expression lived longer. Thus, shortening telomeres may be a cause of aging. 

Variants of TERT may play a role in melanoma by increasing the production of hTERT and promoting unlimited cell proliferation. A variant of TERT may also play a role in PTSD by lowering the enzymatic activity of telomerase. Another variant of TERT may play a role in PTSD by lowering the enzymatic activity of telomerase. One gene variant may reduce TERT activity, which correlates with more severe ADHD.

Telomerase is also abnormally active in most cancer cells (R). 

Lifestyle, diet, and supplement modifications may counteract the effects of these variants by limiting hTERT production and increasing telomerase activity.

The TERT gene provides instructions for making one component of an enzyme called telomerase. Telomerase maintains structures called telomeres, which are composed of repeated segments of DNA found at the ends of chromosomes. Telomeres protect chromosomes from abnormally sticking together or breaking down (degrading). In most cells, telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that they trigger the cell to stop dividing or to self-destruct (undergo apoptosis). Telomerase counteracts the shortening of telomeres by adding small repeated segments of DNA to the ends of chromosomes each time the cell divides.

In most types of cells, telomerase is either undetectable or active at very low levels. However, telomerase is highly active in cells that divide rapidly, such as cells that line the lungs and gastrointestinal tract, cells in bone marrow, and cells of the developing fetus. Telomerase allows these cells to divide many times without becoming damaged or undergoing apoptosis. Telomerase is also abnormally active in most cancer cells, which grow and divide without control or order.

The telomerase enzyme consists of two major components that work together. The component produced from the TERT gene is known as hTERT. The other component is produced from a gene called TERC and is known as hTR. The hTR component provides a template for creating the repeated sequence of DNA that telomerase adds to the ends of chromosomes. The hTERT component then adds the new DNA segment to chromosome ends.

Telomeres are sequences of DNA at the ends of each chromosome. They don’t code for anything; instead, their job is to protect your DNA from damage while it’s being copied. Each time your cells divide, your DNA duplicates, and your telomeres get shorter [R].

When your telomeres are too short to protect your DNA, your cells enter a state called senescence: they stop dividing. Ultimately, if these cells trigger the DNA damage response (DDR), they will be tagged for death [R, R].

Telomerase is an enzyme that adds more nucleotides to the end of the telomere, elongating them. This allows your cells to divide and grow for longer [R].

Researchers have long suspected that shortening telomeres are among the causes of aging. In adult tissues, there isn’t enough telomerase to keep up with cell division. Gradually, over the course of our lifespans, our telomeres get shorter and shorter, and more and more of our cells enter senescence. Thus, older people can’t grow and regenerate their tissues as effectively as younger people [R, R].

Short telomeres have also been linked with degenerative diseases and premature aging in humans. In this light, many researchers have attempted to discover whether activating telomerase and elongating telomeres can prevent or delay aging in humans and animals [R, R, R].

In one memorable study, middle-aged and older mice (one and two years old) were treated with gene therapy that increased their TERT expression. Those that received the treatment lived for 13-24% longer than those without. Best of all? There were no apparent side effects to the procedure [R].

This is important because some research suggests that excess telomerase activity may increase the risk of some types of cancer. For a more complete discussion of telomeres, check out this post.

TERT and Melanoma

The TERT gene codes for hTERT, a part of the telomerase enzyme. Telomerase can protect DNA essential to the production of proteins (genes), by adding non-essential DNA (telomeres) to the ends of condensed DNA structures (chromosomes). This ultimately prevents genes from becoming damaged [R]. 

Within our bodies, cells constantly divide in order to produce more cells. Unfortunately, telomeres shorten in length with every cell division, which can pave the way for DNA damage and consequent cell death [R]. 

While the process of cell division is tightly controlled under normal conditions, cancer cells are able to bypass this regulation in order to divide uncontrollably [R]. 

It’s therefore no surprise that telomerase activity is often elevated in cancer, such as in a form of skin cancer called melanoma [R].

Variants of TERT have been associated with melanoma. These variants may increase the production of hTERT, resulting in excessive telomerase activity and unlimited cell division [R, R, R].

TERT and PTSD

Within our bodies, cells are constantly dividing in order to produce more cells. Unfortunately, telomeres shorten in length with every cell division, which can pave the way for undesired effects arising from DNA damage [R]. 

Although telomere shortening is a normal process associated with aging, psychological stress has been shown to increase the rate at which telomeres shorten, by decreasing the activity of telomerase [R]. 

In line with this, individuals with PTSD have been observed to have shorter telomeres than their healthy counterparts [R].

Shorter telomeres in PTSD have been linked to increased activity of the amygdala, a region of the brain well known to be involved in fear responses. Indeed, PTSD patients often experience symptoms of stress and anxiety in response to events that elicit traumatic, fear-based memories [R].

During brain development, shorter telomeres may inhibit the normal maturation of brain cells. This could lead to altered brain cell connections within regions observed to be affected in PTSD [R].

A variant of TERT has been associated with PTSD. Similar to psychological stress, it’s possible that this variant may lower the enzymatic activity of telomerase, which could promote DNA damage and alter brain cell connectivity within the amygdala. However, this mechanism is largely unclear and requires further research [R]. 

The TERT Gene and ADHD

Chronic stress exposure lowers TERT activity and shortens telomeres [R, R].

Social isolation and ADHD symptoms have been associated with shorter telomeres [R, R].