title: Defective DNA-damage repair induced by nuclear lamina dysfunction is a key mediator of smooth muscle cell aging.
abstract: Accumulation of DNA damage is a major driving force of normal cellular aging and has recently been demonstrated to hasten the development of vascular diseases such as atherosclerosis. VSMCs (vascular smooth muscle cells) are essential for vessel wall integrity and repair, and maintenance of their proliferative capacity is essential for vascular health. The signalling pathways that determine VSMC aging remain poorly defined; however, recent evidence implicates persistent DNA damage and the A-type nuclear lamins as key regulators of this process. In the present review, we discuss the importance of the nuclear lamina in the spatial organization of nuclear signalling events, including the DNA-damage response. In particular, we focus on the evidence suggesting that prelamin A accumulation interferes with nuclear spatial compartmentalization by disrupting chromatin organization and DNA-damage repair pathways to promote VSMC aging and senescence.
authors: BHF Centre of Research Excellence, Cardiovascular Division, King's College London, James Black Centre, 125 Coldharbour Lane, London SE5 9NU, UK. derek.warren@kcl.ac.uk
authors: Derek T
authors: DT
authors: Warren
authors: Catherine M
authors: CM
authors: Shanahan
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D034904:Lamin Type A; D032389:Myocytes, Smooth Muscle / Q000473:pathology*; D034881:Nuclear Lamina / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism
chemical_list: D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A