Genomic instability and vascular aging: A focus on nucleotide excision repair |
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| Authors: | Haiyan Wu Anton J.M. Roks |
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| Affiliation: | 1. Department of Pediatric Nephrology, Wroclaw Medical University, ul. Borowska 213, 50-556 Wroc?aw, Poland;2. Department of Internal Medicine, Occupational Diseases and Hypertension, Clinical Centre of Wroclaw Medical University, Wroclaw, Poland;3. Department of Pathophysiology, Wroclaw Medical University, Wroclaw, Poland;1. Recherche et innovation en chimie médicinale (RICM, ISP-UMR 1282), faculté de pharmacie, université François-Rabelais, 31, avenue Monge, 37200 Tours, France;2. Biocodex, centre de recherche, ZAC de Mercière, chemin d’Armancourt, 60200 Compiègne, France;3. Laboratoire de chimie physique, faculté de pharmacie, université Paris-Descartes, 4, avenue de l’observatoire, case 23, 75006 Paris, France;3. From the Department of Chemistry and Applied Biosciences, Molecular Pharmacology Unit, Swiss Federal Institute of Technology (ETH) Zurich, 8057 Zurich,;4. the Department of Clinical Research, University of Bern, 3010 Bern, and;5. the Department of Medicine, Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland;1. Department of Genetics, Albert Einstein College of Medicine, Bronx, NY;2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY;3. Institute of Aging Research, Guangdong Medical College, Dongguan, China;1. Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Getafe, Spain;2. Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Madrid, Spain;3. Servicio de Geriatría, Hospital Universitario de Getafe, Getafe, Spain |
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| Abstract: | Genomic instability is recognized as one of the primary mechanisms that lead to organismal aging. When genomic maintenance systems, such as nucleotide excision repair, are defective, genomic instability is promoted, which causes accelerated aging (progeria). This can be observed in humans as well as in mouse models of progeroid syndromes. The role of genomic instability related to nuclear DNA is currently under investigation with respect to its role in cardiovascular disease, and in particular those cardiovascular diseases that are associated with vascular aging. In this review, we highlight the first findings in this field of research that come from experiments in nucleotide excision repair-defective mouse models and from genetic studies. Possible mechanisms that mediate the consequences of genomic instability at the local vascular and at the systemic level, such as cell senescence, mutations, mitochondrial damage, and sirtuin 1 and IGF-1 decrease, are discussed and important goals for future research are set. |
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