Telomeres and Telomerase in Ageing and Cancer

Abstract Telomeres are protective structures that cap the ends of linear chromosomes. In humans, they are made of a repetitive DNA (deoxyribonucleic acid) sequence, (TTAGGG) n , and associated proteins. Because DNA polymerases are unable to completely replicate the ends of linear chromosomes, telomeres shorten each time cells divide. This gradual shortening of the telomeres limits their cellular lifespan and contributes to the ageing process. During cancer development, this obstacle to immortality is almost always bypassed by the overexpression of telomerase, a specialised reverse transcriptase that functions to add back telomeric repeats to telomeres. In humans, its expression is limited to rare stem cells of renewal tissues, but a notable exception has been its overexpression in the great majority of cancers. Accordingly, telomerase is being developed as both a novel marker for the detection of cancer cells and a novel target for the treatment of cancers. Herein, we discuss the role of telomeres and telomerase in cancer and ageing, with the emphasis on potential future applications in the treatments of cancers and age‐related diseases. Key Concepts Telomeres are protective structures that cap the ends of chromosomes. Human telomeres are made of TTAGGG DNA repeats and associated proteins. Because of ‘end replication problems’, telomeres shorten each time cells divide, and this shortening limits cellular lifespan and contributes to the ageing process. Telomerase is a specialised reverse transcriptase that functions to add back telomeric repeats to the ends of telomeres, thereby extending cellular lifespan. Telomerase expression in humans is limited to rare stem cells of renewal tissues (gastrointestinal track, blood and skin). Telomerase is almost always aberrantly overexpressed in cancer. This overexpression is detected in 85% of all cancers, irrespective of the tumour type. Telomerase is being developed as a marker to allow the detection of cancer cells in otherwise telomerase‐negative normal tissues. Inhibitors of telomerase are being developed to limit tumour growth and reduce the incidence of recurrences following conventional cancer therapy. Strategies for transient telomerase reactivation are also being developed for the treatment of degenerative diseases and age‐related diseases.