What Are Telomeres?

Telomeres are found on the ends of chromosomes. Our chromosomes consist of DNA wound tightly around spool-like histones. DNA molecules in cells are very long, and packaging them in the form of chromosomes means that they are able to fit in the nuclei of cells. Coiling (also known as “condensing”) the DNA in this way also helps to maintain its integrity because it is less likely to get tangled up.

Human chromosomes look x-shaped when they are fully coiled up, and the ends need to be protected from becoming damaged or fusing with other loose DNA ends (such as the ends of other chromosomes). Telomeres act as protective “caps” on chromosome ends, similar to how the bit of plastic at the end of a shoelace helps to stop it from unravelling.

How Do Telomeres Function?

Telomeres are made up of repeats of a six-base sequence (“bases” are part of the units that form together to create a strand of DNA). They prevent the otherwise free ends of chromosomes from getting tangled and fusing together. By doing this, they ensure that chromosomes are stable and are protected from being degraded.

Every time a cell divides to make two new cells, the telomeres at the ends of the chromosomes within it get shorter. This means that your telomeres shorten as you get older. Once the telomeres become shortened to a particular point the cell stops replicating. It either becomes inactive (“senescent”) or is broken down by a process called apoptosis. This limit to “cellular aging” in turn shortens the lifespan of the organism. This is important, because if “old” cells continue to divide the short telomeres can destabilize the DNA, potentially causing problems such as an extra chromosome, loss of a chromosome or breaks in the chromosomes’ DNA. These can cause a variety of conditions, including cancer.

What Are TBDs?

TBDs are a group of rare inherited conditions that affect how telomeres are maintained. People with this type of condition develop, or are born with, abnormally short telomeres because the telomeres shorten prematurely or at a faster rate than normal. In many cases, the fact that someone has a TBD becomes obvious during their childhood, although it may only start to cause serious problems when they reach adulthood. Children with a TBD can develop bone marrow failure (where the bone marrow does not make enough of different types of blood cells), mouth and skin changes, and have abnormal nails.

Common conditions that indicate that an adult has a TBD include:

• bone marrow failure,
• interstitial lung disease (this term is used to describe a group of conditions that cause scarring of the lungs),
• cirrhosis (scarring of the liver as a result of long-term liver damage) and liver failure, and
• myelodysplastic syndrome (a rare type of blood cancer that affect the bone marrow and the blood cells it produces).

These parts of the body can be particularly affected by TBDs because the cells in them replicate rapidly as part of their normal functioning.

What Treatment Issues Do People with TBDs Have?

As well as the conditions outlined above, adults with TBDs are also at increased risk of developing other cancers, including:

• skin cancers and head and neck tumors,
• hardening of the arteries (blood vessels that transport blood from the heart to other areas of the body),
• complications during pregnancy and
• kidney, dental and/or joint problems.

It is important that patients with these issues are identified correctly as having a TBD if they have one, because they may not respond to a standard treatment in a way that would be expected. In some cases, there may be no response to the treatment at all.

Another issue is that patients who undergo allogeneic stem cell transplantation (allo-SCT) have been reported to have worse outcomes if they have a TBD. allo-SCT is a transplant that replaces bone marrow that is not producing enough healthy blood cells with healthy stem cells (cells that self-renew and can develop into many different cell types) from a donor. It is particularly important that donors for such patients are carefully selected and that the normal treatment regime is adapted for them. Special checkups are also recommended for patients with TBDs who undergo allo-SCT.

What Do the Authors Conclude?

The authors of the review article stress the importance of healthcare professionals – particularly those who specialize in the treatment of conditions that affect the blood, liver, and lungs – being aware of the different ways that TBDs can present. TBDs are considered to be underdiagnosed, particularly when they manifest in adulthood.

Screening of patients in whom a TBD is suspected is essential because people with TBDs need individual and specific treatment approaches. In addition, they are at increased risk of complications that can rapidly become life-threatening and of developing cancer. Adequate counseling of patients and their families is also important because the diagnosis of one person in a family having a TBD has implications for their relatives.

Note: One of the authors of this paper makes a declaration about receiving scientific support. It is normal for authors to declare this in case it might be perceived as a conflict of interest. For more detail, see the Conflict of Interest Statement at the end of the paper.