Defective DNA-damage repair induced by nuclear lamina dysfunction is a key mediator of smooth muscle cell aging

Derek T. Warren, Catherine M. Shanahan

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1780-1785
Number of pages6
JournalBiochemical Society Transactions
Issue number6
Publication statusPublished - 1 Dec 2011


  • Aging
  • DNA-damage repair
  • Nuclear lamina
  • Persistent DNA damage
  • Smooth muscle cell

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