Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks

Nat Cell Biol. 2004 Feb;6(2):168-70. doi: 10.1038/ncb1095.


Humans and animals undergo ageing, and although their primary cells undergo cellular senescence in culture, the relationship between these two processes is unclear. Here we show that gamma-H2AX foci (gamma-foci), which reveal DNA double-strand breaks (DSBs), accumulate in senescing human cell cultures and in ageing mice. They colocalize with DSB repair factors, but not significantly with telomeres. These cryptogenic gamma-foci remain after repair of radiation-induced gamma-foci, suggesting that they may represent DNA lesions with unrepairable DSBs. Thus, we conclude that accumulation of unrepairable DSBs may have a causal role in mammalian ageing.

MeSH terms

  • Aging / genetics*
  • Animals
  • Cell Line
  • Cellular Senescence / genetics*
  • DNA Damage*
  • DNA Repair*
  • Histones / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Telomere / metabolism


  • H2AX protein, human
  • Histones
  • gamma-H2AX protein, mouse