Fig. 2

Telomere shortening: causes and outcomes. Telomeres can shorten due to various factors such as biological aging, cell divisions, obesity, reactive oxygen species (ROS), genotoxic agents, and lifestyle. In this case, telomeres may switch from a closed state to an open state. In the closed state showing normal telomeric structure, not only the double-stranded break (DSB) repair pathways, homologous recombination (HR) and non-homologous end joining (NHEJ), but also DNA damage response mechanism by the actions of ATR and ATM are repressed to prevent telomeres from being sensed as DSBs. In the open state that may appear owing to excessive shortening of telomeres, because of activating the DSB pathways, the possible outcomes involving genomic instability, cellular senescence, apoptosis, and cell cycle arrest may occur. Once short telomeres are elongated to normal lengths by the enzyme telomerase or alternative lengthening of telomeres (ALT) mechanism, cellular functions can be reestablished. This schematic diagram was created using the BioRender Program (BioRenderCompany; Toronto, Canada)