Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening

Figure 1. Oxidative telomere damage or single-strand telomere damage prevents the binding of telomerase and OGG1. Accumulation of oxidative damage on single-strand fragments of telomeres causes a conformation change of the end of chromosome so it cannot be recognized by telomerase (A). OGG1 cannot repair damage on single strand fragments of telomere because it does not have any template for DNA synthesis (B). OGG1–8–oxoguanine DNA glycosylase; ROS–reactive oxygen species.

Figure 2. Molecular pathways of telomere shortening and SASP expression. Intermittent hypoxia generates a increased amount (↑) of ROS and develops oxidative stress. ROS damages many cellular components such as lipids or DNA, which activate the NF-κβ complex. NF-κβ is translocated to the nucleus where its function is the translation of many genes including SASP phenotypes. Oxidative DNA damage causes telomere shortening directly by interference with the DNA structure. CD36—scavenger receptor; CXCLs—C-X-C motif chemokine ligands; GATA4—GATA binding protein 4; GM-CSF—granulocyte-macrophage colony-stimulating factor; ICAM-1—intercellular adhesion molecule 1; IKK—kinase of Iκβ; IL1—interleukin 1; IL6—interleukin 6; IL8—interleukin 8; MMPs—metalloproteinases; NF-κβ—nuclear factor κβ; oxoLDL—oxidative law-density lipoprotein; ROS—reactive oxygen species; SASP—senescence associated secretory phenotype; TGFB1—transforming growth factor β1; TNF—tumor necrosis factor; MMPs—metalloproteinases; GM-CSF—granulocyte-macrophage colony-stimulating factor.