Telomeres Shortening: A Mere Replicometer?

Abstract

Telomeres are protective structures at the ends of linear chromosomes that play an important role in maintaining genomic stability. Telomere shortening, which occurs with each round of cell division, leads to a permanent proliferation arrest, also known as replicative senescence. This process has been shown to have important implications in vivo as an increase in the frequency of senescent cells occurs in mammalian tissue with age and in a variety of age-related diseases. Telomeres possess unique features, namely the presence of telomere-binding proteins collectively known as “shelterin”, that equally prevent telomere end-to-end fusions and the repair of damage induced by extrinsic and intrinsic stress. This inability to repair damage contributes to the activation of a persistent DNA damage response, which has been shown to be important in the establishment of cellular senescence. Evidence suggests that telomeres not only limit the proliferative potential of cells, but also act as highly sensitive sensors of stress in cells. This may be a protective mechanism against cancer, but also contribute to tissue dysfunction observed during ageing.