Uncapping of telomeres leads to chromosome abnormalities Telomere Biology Diagrams In this review, we describe how telomere uncapping potentially leads to age-related vascular dysfunction and increased cellular senescence, oxidative stress, and inflammation. Importantly, we present evidence to argue that telomere uncapping is more biologically relevant than telomere shortening and a better marker of vascular aging and target Since then, great advances have been made in the understanding of how telomeres are able to signal the senescence arrest. These mechanisms are of particular importance in the field of ageing, since cellular senescence, driven by telomere dysfunction, has been shown to be a causal driver of ageing and age-related pathology (van Deursen, 2014). 1.1.
VSMCs in human atherosclerotic plaques show cellular senescence markers and telomeres that are markedly shorter than those in unaffected vessels from the same individual 115. Telomere dysfunction induced by VSMC-specific expression of mutant TRF2 is sufficient to increase atherosclerosis 116,117.
related arterial telomere uncapping and senescence is greater in ... Biology Diagrams
Next, we investigated the mechanisms by which FBW7 mediates stress-induced cell senescence. The telomere shelterin protein TPP1 was found to be significantly unstable in the presence of H 2 O 2, BLM, or IR, undergoing rapid degradation in human pulmonary A549 cells (Figure 2 A). Having confirmed the specificities of detecting shelterin proteins TPP1, TIN2, TRF1, TRF2, and Rap1 using
However, it is important to remember that telomere uncapping and cellular senescence have critical physiological roles. Recapping telomeres has never been demonstrated experimentally and may lead to the division of cells with damaged DNA. In contrast, age-related telomere uncapping may result directly from a dysfunctional shelterin complex, in Environmental stressors such as bacterial toxins and radiation can cause premature aging and fibrosis. Wang et al. reveal that in mice exposed to radiation or the bacterial toxin bleomycin, the tumor suppressor protein FBW7 marks the telomere protein TPP1 for degradation, triggering telomere uncapping and shortening, cancer or stem cell aging, and pulmonary fibrosis. Targeting FBW7 by an 8-mer
Telomere uncapping and vascular aging Biology Diagrams
4.1. Sex differences in telomere uncapping and senescence. We have previously demonstrated in arteries that telomere uncapping increases with advancing age in a combined group of women and men (Morgan et al., 2013). In the present study, we demonstrate that arterial telomere uncapping was significantly greater with age in women, but not men.
