Telomere uncapping and vascular aging.

While most telomere biology research continues to focus on telomere shortening, there is increasing evidence that telomere deprotection, or "uncapping", is more biologically and possibly clinically important. Telomeres form t-loops to prevent the chromosome ends from appearing as a double-stranded DNA break and initiating a DNA damage response. Breakdown of the t-loop structure, referred to as uncapping, can lead to cellular senescence and increased oxidative stress and inflammation in tissues. In this review, we will describe how telomere uncapping potentially leads to age-related vascular dysfunction, and increased cellular senescence, oxidative stress, and inflammation. Importantly, we will present evidence to argue that telomere uncapping is more biologically relevant than telomere shortening, and a better marker of vascular aging and target for anti-aging interventions.

KEYWORDS: Aging; Endothelial; Senescence; Telomere; Vascular

PMID: 29547021 DOI: 10.1152/ajpheart.00008.2018