Telomeres: at the heart of the aging process

What are telomeres?

In the nucleus of each of the billions of cells that compose our bodies, chromosomes make up DNA. At the end of every chromosome, you can find small structures called telomeres. They progressively get shorter with time, and their length can be linked to age.

Telomeres are ribonucleoprotein complexes found at the extremities of chromosomes. They correspond to tandem repetitions of nucleotide sequences (TTTAGG) that shrink with each cellular replication. Throughout life, cells multiply. They accumulate cycles of division and replication, in order to renew damaged cells and tissue. In an aged organism, that is when telomere shortening occurs [1]. In this article, we will be looking at the way telomeres work and at the impact of their shortening on the body as a whole.

Aging, and the role of telomeres

Telomere shortening is directly linked to cell division. Because DNA polymerase cannot replicate the linear end of chromosomes, with DNA each replication cycle, there is a loss of some genetic material [1]. Since telomeres don’t contain coding sequences, no genetic information is lost. Therefore, telomeres are implicated in genome integrity preservation processes and are indispensable to cellular function.

When no mechanism intervenes to regenerate telomeres, and since telomere shortening occurs with each cell replication cycle, it indicates that cells cannot live indefinitely. The Hayflick limit is the maximum number of cell divisions that a cell can undergo [2]. It allows to relate telomere length to the lifespan of the cell.

Telomeres can trigger senescence, which is a cause of aging

The shorter telomeres become, the bigger the risk to lose some genomic information during the next cell division, inducing major cell dysfunction. That is why, with somatic cells, when telomeres reach the “critical” Hayflick limit, response pathways are activated in order to fix potential DNA damage. When these pathways are activated, the cell cycle is stopped, which can lead to cell senescence or death [3].

Throughout the aging process, cells accumulate multiple mitotic divisions which makes the risk of developping genetic anomalies rise. Telomeres then prevent the development of these damaged cells. Their measurement could give us information about the speed at which aging occurs, as well as about their biological age.

We call telomeres the “biological clockS” of our bodies.

Telomeres against tumor cells

Tumor cells are somatic cells that have malfunctioned as they develop and multiply very quickly. Their proliferation triggers a great number of cell divisions and consequently accelerates telomere shortening. The telomeres in these cells then quickly reach the Hayflick limit, which triggers the process previously described. This stops the cell cycle and sends the tumor cell into senescence. Cell proliferation is then stopped.

Telomere shortening occurs in the processes that prevent tumor cells from proliferating [3]. This normally allows to eliminate tumors before they become malignant and cancerous.

Telomeres and stem cells: aging essentials

There are mechanisms to maintain telomere structure that allow to prolong the life of some cells. Among them is the telomerase. This enzyme helps to synthesize telomeres [2].

Telomerase is absent from most of the organism’s cells. It is active in stem cells such as HSC, NSC and ESC: hematopoietic stem cells, neural stem cells, and epidermal stem cells. These cells are mainly involved in tissue renewal processes.

Telomerase allows these specific cells to last in time while remaining functional. Accumulation of telomere malfunctions in these types of cells could trigger tissue and organ degenerescence, one of the main characteristics of aging. In the fight against aging, firm knowledge of the biological mechanisms involving telomerase then seem indispensible.

Telomere shortening: diseases linked to aging

Telomerase modifications lead to accelerated telomere shortening. This results in the apparition of diseases such as dyskeratosis congenita, which affects tissues that need fast and constant cellular renewal, or like aplastic anemia, that decreases the amount of blood cells [2]. These diseases are often associated with poor tissue and cell renewal, and their symptoms are fairly similar to those of aging.

Telomere length and telomerase therefore seem central to the aging process. This is why it would be interesting to include telomere measurement when developing a metrology of aging.

Sources :

[1] Chatterjee, S. (2017). Telomeres in health and disease. Journal of Oral and Maxillofacial Pathology, [online] 21(1), p.87. DOI : 10.4103/jomfp.JOMFP_39_16. [Accessed 22 May 2017].

[2] Blasco, M. (2007). Telomere length, stem cells and aging. Nature Chemical Biology, [online] 3(10), pp.640-649. DOI :10.1038/nchembio.2007.38 [Accessed 22 May 2017]

[3] Shay, J. (2016). Role of Telomeres and Telomerase in Aging and Cancer. Cancer Discovery, [online] 6(6), pp.584-593. DOI :  10.1016/j.semcancer.2011.10.001 [Accessed 22 May 2017].