Why do telomeres shorten?

Why do telomeres shorten

Telomeres play an important role in protecting our chromosomes, but as we age, they decrease in length. In this blog we explore how and why telomeres shorten.

Telomere structure

Human telomeres are made up of thousands of repeats of the same DNA sequence (TTAGGG), bound by a special set of proteins called shelterin.

They are located at the end of our chromosomes and act to prevent damage or fusion with other chromosomes.

As cells divide, the genetic material coded for on chromosomes is read and copied, in order to produce a replicated version for each new daughter cell.

However, the very end tip of the chromosomes cannot be copied and gets lost each time the genetic material is replicated. Sporadic loss of telomere repeats can also occur due to damage.

The telomere acts as a buffer to ensure the important genetic information coded for on the chromosome is completely copied for each new cell and protected from damage.

Over time, this results in fewer and fewer DNA repeats making up the telomeres after each cell division i.e. gradually the telomeres shorten.

Telomere shortening

It is natural that telomeres shorten as we grow and age. However, some people have abnormally short telomeres throughout their life. Some can experience an accelerated telomere shortening process.

The incidence of very short telomeres is associated with cell senescence (halting of cell division). Most cells in our body (somatic cells) have a finite number of divisions and therefore a limited capacity to proliferate.

Over time the cell loss, or the accumulation of senescent cells, caused in part by critically short telomeres can result in organ and tissue dysfunction. Or in other words, biological aging. Thus, shortening telomeres can be considered a biomarker for aging.

Short telomeres have been associated with a range of conditions called telomere biology disorders (TBDs) and likened to accelerated aging, for example dyskeratosis congenita (DC), pulmonary fibrosis (PF) and chronic obstructive pulmonary disease (COPD).

In TBDs the extension (during early development), efficient replication or maintenance of telomere length or structure is affected. This can impact many different systems and organs within the body.

Read more about TBDs here or watch this video explaining TBDs.

As telomeres protect chromosomal genetic material, senescence can guard against unrestricted growth of damaged cells. This can be an important safeguard against cancer (tumor growth).

There are several mechanisms and agents that may be able to affect telomere length.

For example, the enzyme telomerase can synthesize the TTAGGG DNA repeats that make up telomeres and therefore acts to maintain telomere length. You can read more about telomerase and how it works here.

Strategies to enhance telomerase activity or enable its access to telomeric DNA to restore telomere length are being explored in research studies that could one day be used to treat TBDs.

On the other hand, therapies to block telomerase activity and / or aiming to reduce telomere length could be useful in cancer treatment to limit tumor growth. These approaches have been explored but have been challenging with regards to effect speed and toxicities.

To find out more about how telomeres shortening can impact our health, and how telomere length can be measured, look at this section of our website.

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