title: Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction.
abstract: The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS) leads to oxidative stress, loss of nitric oxide (•NO) signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here discuss the importance of different sources of ROS for vascular aging and their contribution to the increased cardiovascular risk in the elderly population with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA. Also the interaction (crosstalk) of mitochondria with nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases is highlighted. Current concepts of vascular aging, consequences for the development of cardiovascular events and the particular role of ROS are evaluated on the basis of cell culture experiments, animal studies and clinical trials. Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging) than for the maximal lifespan.
authors.affiliation: Medical Clinic, Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany. yuliya.mikhed@unimedizin-mainz.de.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Mikhed
authors.affiliation: Medical Clinic, Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany. daiber@uni-mainz.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Daiber
authors.affiliation: Medical Clinic, Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany. sebastiansteven@gmx.de.|Center for Thrombosis and Hemostasis, Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany. sebastiansteven@gmx.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Steven
mesh_terms: D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species
keywords: aging; mitochondrial DNA damage; mitochondrial oxidative stress; vascular dysfunction