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.
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December 2011
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Conference Article|
November 21 2011
Defective DNA-damage repair induced by nuclear lamina dysfunction is a key mediator of smooth muscle cell aging
Derek T. Warren;
Derek T. Warren
1
1BHF Centre of Research Excellence, Cardiovascular Division, King's College London, James Black Centre, 125 Coldharbour Lane, London SE5 9NU, U.K.
1To whom correspondence should be addressed (email derek.warren@kcl.ac.uk).
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Catherine M. Shanahan
Catherine M. Shanahan
1BHF Centre of Research Excellence, Cardiovascular Division, King's College London, James Black Centre, 125 Coldharbour Lane, London SE5 9NU, U.K.
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Publisher: Portland Press Ltd
Received:
August 10 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (6): 1780–1785.
Article history
Received:
August 10 2011
Citation
Derek T. Warren, Catherine M. Shanahan; Defective DNA-damage repair induced by nuclear lamina dysfunction is a key mediator of smooth muscle cell aging. Biochem Soc Trans 1 December 2011; 39 (6): 1780–1785. doi: https://doi.org/10.1042/BST20110703
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