Advanced research in telomeres and disease risk

Telomeres are specialized structures localized at the very ends of human chromosomes whose primary function is to prevent a cell from sensing linear chromosome ends as breaks in the DNA. Telomeres are composed of a long sequence of TTAGGG, which together with specialized proteins, form a cap like structure, suppressing the activation of DNA damage response (DDR). They were first described in 1938 and further investigation led to the discovery of an intracellular enzyme which was responsible for telomere elongation. This enzyme works as a reverse transcriptase and it is called “telomerase.” Both telomere and telomerase are required for preserving genome integrity and stability. Due to the “end replication problem” and telomerase repression, in most normal human somatic cells, telomeres progressively shorten with each cell division and replication event, leading to replicative cellular senescence. Telomere shortening has been proposed to function as a “mitotic clock” that measures how many times a cell has divided (Sfeir et al. 2005, De Lange 2002), and it can be accelerated by many factors such as inflammation and oxidative stress (Zhang et al. 2015).