Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1863, Issue 2, Pages 360-367Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2015.11.034
Keywords
Shelterin; DNA damage; Senescence; Telomere dysfunction; Aging
Categories
Funding
- Austrian Science Fund FWF [J3064]
- Association for the Promotion of Research on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB)
- Ludwig Boltzmann Cluster for Cardiovascular Research
- Austrian Science Fund (FWF) [J3064] Funding Source: Austrian Science Fund (FWF)
Ask authors/readers for more resources
Aging is a major factor predisposing for multiple diseases. Telomeres at the ends of chromosomes protect the integrity of chromosomal DNA. A specialized six-protein complex termed shelterin protects the telomere from unwanted interaction with DNA damage pathways. The aim of our study was to evaluate the integrity of telomeres and the stability of telomere protection during aging in endothelial cells (EC). We describe that aging EC can be characterized by an increased cell size (40%, p = 0.02) and increased expression of PAI 1 (4 fold, p = 0.02), MCP1 (10 fold, p = 0.001) and GMCSF (15 fold, p = 0.004). Telomeric state in aging cells is defined by an increased telomere oxidation (27%, p = 0.01), reduced telomere length (62%, p = 0.02), and increased DNA damage foci formation (5% in young EC versus 16% in aged EC, p = 0.003). This telomeric dysfunction is accompanied by a reduction in the shelterin component TRF1 (33% mRNA, p = 0.001; 24% protein, p = 0.007). Overexpression of TRF1 in aging EC reduced telomere-associated DNA damage foci to 5% (p = 0.02) and reduced expression levels of MCP1 (18% reduction, p = 0.008). Aged EC have increased telomere damage and an intrinsic loss of telomere protection. Reestablishing telomere integrity could therefore be a target for rejuvenating endothelial cell function. (C) 2015 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available