title: Genomic instability and vascular aging: a focus on nucleotide excision repair.
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.
authors: Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus Medical Center Rotterdam, Erasmus University Rotterdam, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors: Haiyan
authors: H
authors: Wu
authors: Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus Medical Center Rotterdam, Erasmus University Rotterdam, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. Electronic address: a.roks@erasmusmc.nl.
authors: Anton J M
authors: AJ
authors: Roks
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics*; D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D005819:Genetic Markers; D042822:Genomic Instability; D006801:Humans; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics; D010641:Phenotype; D012307:Risk Factors; D014652:Vascular Diseases / Q000235:genetics* / Q000503:physiopathology
chemical_list: D005819:Genetic Markers