Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing

Curr Opin Genet Dev. 2014 Jun:26:89-95. doi: 10.1016/j.gde.2014.06.009. Epub 2014 Aug 11.

Abstract

The DNA damage response (DDR) orchestrates DNA repair and halts cell cycle. If damage is not resolved, cells can enter into an irreversible state of proliferative arrest called cellular senescence. Organismal ageing in mammals is associated with accumulation of markers of cellular senescence and DDR persistence at telomeres. Since the vast majority of the cells in mammals are non-proliferating, how do they age? Are telomeres involved? Also oncogene activation causes cellular senescence due to altered DNA replication and DDR activation in particular at the telomeres. Is there a common mechanism shared among apparently distinct types of cellular senescence? And what is the role of telomeric DNA damage?

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / genetics*
  • Animals
  • Cellular Senescence / genetics*
  • DNA Damage*
  • DNA Repair / genetics*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Humans
  • Models, Genetic
  • Signal Transduction / genetics*
  • Telomere / genetics